CN1854128A - Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds - Google Patents

Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds Download PDF

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CN1854128A
CN1854128A CNA2006100824810A CN200610082481A CN1854128A CN 1854128 A CN1854128 A CN 1854128A CN A2006100824810 A CNA2006100824810 A CN A2006100824810A CN 200610082481 A CN200610082481 A CN 200610082481A CN 1854128 A CN1854128 A CN 1854128A
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diamino
cyclohexane
cis
dimethyl
phenanthroline
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CN1854128B (en
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S·L·布克瓦德
A·克拉帕斯
J·C·安蒂拉
G·E·乔布
M·沃尔特
F·Y·邝
G·诺尔德曼
E·J·亨尼斯
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Massachusetts Institute of Technology
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Abstract

The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of an amide or amine moiety and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In additional embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between a nitrogen atom of an acyl hydrazine and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In other embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of a nitrogen-containing heteroaromatic, e.g., indole, pyrazole, and indazole, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-oxygen bond between the oxygen atom of an alcohol and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. The present invention also relates to copper-catalyzed methods of forming a carbon-carbon bond between a reactant comprising a nucleophilic carbon atom, e.g., an enolate or malonate anion, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. Importantly, all the methods of the present invention are relatively inexpensive to practice due to the low cost of the copper comprised by the catalysts.

Description

The formation of copper-catalytic carbon-heteroatom bond and C-C
The application is dividing an application of application number is 02812587.8, the applying date is on April 24th, 2002 patent application.
Background technology
N-arylamines and acid amides natural product and Chemicals, as medicine, the important basic structure in dyestuff and the agricultural prods.At present, the palladium catalysis method that is used for the N-arylation of amine and acid amides is widely used in medicine, has the material of important electronics character and synthesizing of arylamines in the original metal catalyzer ligand and N-arylamide.Similarly, the coupling of formation C-C also is widely used between palladium-catalytic aryl or vinyl halide and the carbon nucleophile.Referring to, for example, Stille, J.K.Angew.Chem., Int.Ed.Engl., 25:508-524 (1986); Miyaura, N.et al., Chem.Rev., 95:2457-2483 (1995); Negishi, E.Acc.Chem.Res., 15:340-348 (1982).
But the ever-increasing cost of palladium has reduced the magnetism of these effective ways.Therefore, need to explore a kind of being used for from the catalysis process high with efficient of the routine of aryl halide and corresponding amine and synthetic N-arylamines of acid amides and acid amides, this method should not comprise rare, expensive transition metal based on a kind of, as the catalyzer of palladium.Similarly, need to explore a kind of catalysis process high with efficient that is used for forming the routine of C-C between aryl or vinyl halide and carbon nucleophile, this method should not comprise rare, expensive transition metal based on a kind of, as the catalyzer of palladium.
1998, the price of international metal market batch palladium roughly was 5,000 times of batch copper cost.Therefore, based on catalyst costs, if above-mentioned transformation can use copper to replace palladium as catalyzer, the magnetism of so this transformation will improve greatly.
Brief summary of the invention
The present invention relates to the synthetic method of copper-catalytic carbon-heteroatoms and C-C.In some concrete scheme, the present invention relates to the nitrogen-atoms and the aryl of copper-catalytic acid amides or amine groups, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonate.In other concrete scheme, an invention relates to the nitrogen-atoms and the aryl of copper-catalytic acylhydrazine, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonate.In other concrete schemes, an invention relates to copper-catalytic nitrogenous heteroaryl, for example, and indoles, the nitrogen-atoms of pyrazoles and indazole and aryl, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonate.In some concrete scheme, the present invention relates to the Sauerstoffatom and the aryl of the catalytic alcohol of copper, heteroaryl, or the synthetic method of the carbon-oxygen bond between the activated carbon of vinyl halide or sulphonate.The present invention also relates to copper-catalytic reagent that comprises the nucleophilic carbon atom, for example, enolate or malonate negatively charged ion, with aryl, heteroaryl, or the synthetic method of the C-C between the activated carbon of vinyl halide or sulphonate.Importantly, because catalyzer comprises copper cheaply, it is all relatively inexpensive to implement all methods of the present invention.
Brief description of the drawings
Fig. 1 the tabulate result of copper-catalytic benzylamine arylation of show using aryl iodide and the reaction conditions that uses.
Fig. 2 the tabulate result of copper-catalytic various amine arylations of show using phenyl-iodide and the reaction conditions that uses.
Fig. 3 the tabulate result of copper-catalytic various amine arylations of show using various aryl iodides and the reaction conditions that uses.
Fig. 4 tabulates and show to use the copper-catalytic bromobenzene amination as ligand of n-hexyl amine and various substituted phenol.
Fig. 5 tabulates and shows the copper-catalytic 1-bromo-3 that uses n-hexyl amine and various copper complexes, the amination of 5-dimethylbenzene.
Fig. 6 tabulates and shows the copper-catalytic 1-bromo-3 that uses the n-hexyl amine in all kinds of SOLVENTS, the amination of 5-dimethylbenzene.
Fig. 7 tabulates and shows copper-catalytic bromobenzene amination of using n-hexyl amine and various ligands.
Fig. 8 tabulates and shows the copper-catalytic 1-bromo-3 that uses n-hexyl amine and various solvent-free ligands, the amination of 5-dimethylbenzene.
Fig. 9 tabulates and shows the copper-catalytic 1-bromo-3 that makes the n-hexyl amine with low catalyst loading, the amination of 5-dimethylbenzene.
The tabulate copper-catalytic amination of the aryl bromide that shows various functionalization of Figure 10.
Figure 11 tabulates demonstration copper-catalytic various adjacent replacements, dibromo that replace with the amination heterocyclic aryl bromide.
The tabulate amination of aryl bromide of copper-catalytic various functionalization of show using various solvent-free amine of Figure 12.
Figure 13 tabulates and shows the arylation of the indoles in the copper-catalytic dioxane that uses 4-toluene bromide and various ligands.
Figure 14 tabulates and shows the arylation of the indoles in the copper-catalytic toluene that uses 4-toluene bromide and various ligands.
Figure 15 tabulates and shows the arylation of the indoles in the copper-catalytic toluene that uses 2 bromo toluene and various ligands.
Figure 16 tabulates and shows the arylation of the indoles in the copper-catalytic toluene that uses 2 bromo toluene and various ligands.
Figure 17 tabulates and shows use 3, the arylation of the N-phenylacetamide in the copper of 5-dimethyl benzene iodide and various ligands-catalytic dioxane.
Figure 18 tabulates and shows use 3, the arylation of the 2-Pyrrolidone in the copper of 5-dimethyl benzene iodide and various ligands-catalytic toluene.
Figure 19 tabulates and shows use 3, the arylation of the N-benzyl methane amide in the copper of 5-dimethyl benzene bromide and various ligands-catalytic toluene.
Figure 20 tabulates and shows use 3, the arylation of the N-methylformamide in the copper of 5-dimethyl benzene iodide and various ligands-catalytic toluene.
Figure 21 tabulates and shows use 3, the arylation of the N-methylformamide in the copper of the copper in 5-dimethyl benzene iodide and various sources-catalytic toluene.
Figure 22 tabulates and shows the arylation of the N-methyl para toluene sulfonamide in the copper-catalytic toluene that uses phenyl-iodide and various alkali.
Figure 23 tabulates and shows the arylation of use diethyl salicylic amide as the n-hexyl amine among the copper-catalytic DMF of ligand and various alkali.
Figure 24 tabulates and shows and to make the arylation of spent glycol as the benzylamine in the copper-catalytic Virahol of ligand and various alkali.
Figure 25 tabulates and shows the arylation of the various glycol of use as the benzylamine in the copper-catalytic Virahol of ligand.
Figure 26 tabulates and shows the arylation of the n-hexyl amine in the copper-catalytic propyl carbinol that uses various ligands.
Detailed description of the invention
The present invention relates to the synthetic method of carbon-hetero atom and the carbon-carbon bond of copper-catalysis. In some concrete scheme, the present invention relates to the acid amides of copper-catalysis or nitrogen-atoms and the aryl of amine groups, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonic acid ester. In other concrete scheme, an invention relates to nitrogen-atoms and the aryl of the acid hydrazide of copper-catalysis, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonic acid ester. In other concrete schemes, an invention relates to the nitrogen-containing hetero aryl of copper-catalysis, for example, and indoles, pyrazoles, and the nitrogen-atoms of indazole and aryl, heteroaryl, or the synthetic method of the carbon-nitrogen bond between the activated carbon of vinyl halide or sulphonic acid ester. In some concrete scheme, the present invention relates to oxygen atom and the aryl of the alcohol of copper catalysis, heteroaryl, or the synthetic method of the carbon-oxygen bond between the activated carbon of vinyl halide or sulphonic acid ester. The present invention also relates to the reactant that comprises the nucleophilic carbon atom of copper-catalysis, for example, enolate or malonate anion, with aryl, heteroaryl, or the synthetic method of the carbon-carbon bond between the activated carbon of vinyl halide or sulphonic acid ester.
Importantly, because catalyzer comprises copper cheaply, it is all relatively inexpensive to implement all methods of the present invention.
Copper-catalytic acid amides N-arylation
The coupling of aryl iodide and bromide and acid amides, promptly so-called Goldberg reaction, its substrate scope does not have very general foundation, usually needs the copper complex of stoichiometric quantity.And as the situation of Ullmann reaction, the reaction conditions of Goldberg reaction is usually quite harsh, and the temperature that needs is up to 210 ℃.Yet 1mol%CuI is only used in these reactions of the inventive method catalysis, has successfully used as few as the CuI of 0.2mol%.In many examples, be derived from 1%CuI, 10% (racemic)-anti--hexanaphthene-1,2-diamines, and K 3PO 4Or Cs 2CO 3System provide excellent catalyzer for the amidation of aryl iodide.Importantly, CuI is copper (I) source of air-stable.As the illustration that can introduce, with respect to the aryl iodide component, this method can be used substrate widely.Especially, the arylation of the substrate that contains 2 ° of acid amides of 4-Iodoaniline is possible; The catalytic C-N of Pd-that contains the substrate of these functional groups is bonded to not success of method.We also can N-virtueization N-BOC hydrazine.Further, this provides a kind of synthetic method of suitable hydrazine, and, therefore the Fischer indoles substrate that produces and the catalysis process of other heterocycle synthons.
Copper-catalysis process of the present invention provides the amidation of aryl bromide.The general 1-20mol%CuI that uses of these reactions; For example, in a concrete scheme, use 1mol%CuI, product yield is 90%.In addition, the coupling of non-activated aryl chloride and acid amides also can use the inventive method to finish.
The inventive method also is applicable to the coupling of aryl iodide and primary amide; In fact, to acyl substituent (RC (O) NH 2In R) as if without limits.With respect to 2 ° of acid amides, N-anilid and lactan are preferred substrates.The N-formyl radical acid amides that is derived from alkylamine is gratifying substrate.Therefore, we believe the result of this method of steric influence.In the concrete scheme of ligand arylation and substrate arylation competition therein, use 1,10-phenanthroline or N, N '-dimethyl-1, the 2-diamines shows improved result.
In preferred version, be 20-25 by the specified range of the acid amides pka of DMSO metering.Usually, the highly basic in the inventive method is more effective unlike weak base; For example, Cs in many concrete schemes 2CO 3And K 3PO 4Be efficient alkali.For the coupling of aryl bromide when low catalyst loads and the coupling of aryl chloride, use K 2CO 3Be preferred.These results are consistent with the lower concentration prevention catalyst deactivation important concept that keeps the protonated acid amides of removal.Enjoyably, to a certain extent, reduce the catalyzer loading and seem not sacrifice reaction efficiency.
Copper-catalytic heterocyclic N-arylization
According to the needs of this product, the most important substrate of some of catalytic N-arylation is a nitrogen heterocyclic ring, for example, and pyrroles, and indoles.
The heterocyclic N-arylization of the copper of report mediation in the past is subjected to being similar to the restriction of Ullmann reaction.Similarly, the scope of the coupling of copper promotion or catalytic heterocycle and aryl boric acid also is limited.And, boric acid as the magnetism of precursor than aryl halide much less.Correspondingly, heterocyclic arylization has been the problem that people explore for many years.
The inventive method provides uses 2-halo phenylmethylether or the 2 methyl indole N-arylation method as the nitrogenous heteroaryl of mating partner; In these concrete schemes, the inventive method almost provides required product quantitatively, and same transformation is difficult to use palladium catalyst.
Further, the inventive method can make pyrazoles and indazole N-arylation.
Correspondingly, the inventive method can make various nitrogen heterocyclic arylations.
Figure A20061008248100441
In these changed, gentle, cheap alkali was as K 3PO 4And K 2CO 3, be effective.These reactions are cleaned usually very much, and the reduction of aromatic hydrocarbons generally than corresponding palladium system problem still less.In the inventive method, mostly just use the 1mol% cuprous iodide just can cause required coupling; But this reaction needs the temperature of rising, for example 110 ℃ usually.Yet in some concrete scheme, the inventive method provides the N-aryl heteroarylization of good yield when at room temperature carrying out.
Definition
For convenience's sake, be used for specification sheets, some term of embodiment and additional claim is collected in here.
Term " nucleophilic reagent " is known in this field, and the chemical reagent of reactive electron pair represented to have in this term used in this application.The example of nucleophilic reagent comprises uncharged compound such as water, amine, mercaptan and alcohol, and charged compound such as alkoxide, thiolate, carbanion and various organic and inorganic anion.Typical anionic nucleophilic reagent comprises simple negatively charged ion such as oxyhydroxide, trinitride, prussiate, thiocyanate-, acetate, formate or chlorocarbonate, and hydrosulphite.Organometallic compound such as organic copper, organic zinc, organolithium, Grignard reagent, enolate, acetylide, etc., under appropriate reaction conditions, can be suitable nucleophilic reagent.When substrate need reduce, hydride also may be suitable nucleophilic reagent.
Term " electrophilic reagent " is well known in the art, refers to accept from definition nucleophilic reagent as above the chemical reagent of a pair of electronics.The electrophilic reagent that is used for the inventive method comprises ring compound such as epoxide, ethylenimine, episulfide, cyclic sulfuric ester, carbonic ether, lactone, lactan etc.Acyclic electrophilic reagent comprises sulfuric ester, sulphonate (for example tosylate), and muriate, bromide, iodide, etc.
Term used in this application " atom of parent's electricity ", " electrophilic center " and " reactive center " relates to the atom of being attacked and form new key by nucleophilic reagent.Under great majority (yet being not whole) situation, it also is the atom of leavings group from its disengaging.
Term used in this application " electron withdrawing group " is being known in the art, and it attracts electronics to surpass hydrogen atom to the functionality of itself to be illustrated in same position.The example of electron withdrawing group comprises nitro, ketone, and aldehyde, alkylsulfonyl, trifluoromethyl ,-CN, muriate, etc.Term used in this application " electron-donating group " be illustrated in same position its attract electronics to the functionality of itself less than hydrogen atom.The example of electron-donating group comprises amino, methoxyl group, etc.
Term " Lewis base " and " Lewis base " are being known in the art, and relate to the chemical reagent that can provide electronics under some reaction conditions.
The example of Lewis base comprises uncharged compound such as alcohol, mercaptan alkene, and amine, and charged compound such as alkoxide, thiolate, carbanion and various other organic anions are arranged.
Term " brnsted base " is that this is known, refers to uncharged atom or molecule, oxide compound for example, amine, alkoxide, carbonate, just proton acceptor.
Term " Lewis acid " and " lewis acidic " are well known in the art, relate to the chemical reagent that can accept a pair of electronics from Lewis base.
Term " meso compound " is being known in the art, represents minimumly to have two chiral centres but because inner plane, or point symmetry and be achiral compound.
Term " chirality " refers to its mirror image mating partner is had the molecule of nonadditivity, and term " achiral " refers to its mirror image mating partner is had the molecule of additivity." prochiral molecule " has achiral molecule of the potential that becomes chiral molecules in special method.
Term " steric isomer " refers to have identical chemical constitution, but its atom or the different compound of group spatial disposition.Especially, term " enantiomorph " refers to two of the compound steric isomers of non-superimposable mirror image each other.On the other hand, term " diastereomer " refers to comprise two or more asymmetric centers and the relation of a pair of steric isomer of mirror image each other not.
In addition, " stereospecific method " is the method that a kind of generation is better than the special steric isomer of other possible steric isomer products." mapping system of selection " a kind of to help a kind of method among two possible enantiomorphs of production reaction product.This method be considered to produce " three-dimensional selectively enrichment " product (for example mapping selectively enrichment or selectively enrichment of non-mapping), with respect to do not have chiral catalyst in the presence of the productive rate of the steric isomer that produces of same reaction, a kind of special steric isomer of product has statistics and goes up the bigger productive rate of significance.For example, will be obtained enantiomeric excess by the catalytic mapping selective reaction of a kind of chiral catalyst than the more special enantiomorph of the reaction that lacks chiral catalyst.
Term " regional isomer " refers to wherein have same molecular formula but the different compound of the connection of atom.Correspondingly, " regional selection method " is the method that helps production special region isomer, for example, produces the reaction that statistics goes up a certain regional isomer of significance advantage.
The compound that term " reaction product " expression is produced by nucleophilic reagent and substrate reactions.In general, term used in this application " reaction product " refers to stable, separable compound, rather than unsettled intermediate or transition state.
According to the present invention, term " substrate " be used for expression can with nucleophilic reagent, or ring extension reagent react obtains at least a compound with product of a three-dimensional origin center.
Term " catalytic amount " is being known in the art, and represents a kind of inferior stoichiometric quantity with respect to reagent.
The reaction of the present invention's expection that hereinafter will discuss more fully comprises the mapping selection, and non-mapping is selected, and/or regional selective reaction.The mapping selective reaction is the reaction that achiral reagent is changed into the chiral product of an enantiomorph enrichment.Enantioselectivity is (ee) to measure according to " enantiomeric excess " usually, is defined as follows:
% enantiomeric excess A (ee)=(% enantiomorph A)-(% enantiomorph B)
Wherein A and B are the enantiomorphs that forms.Comprise " optical purity " or " specific rotation " with the common other term that uses of enantioselectivity.The mapping selective reaction obtains enantiomeric excess greater than zero product.The mapping selective reaction preferably obtains enantiomeric excess greater than 20% more preferably greater than 50%, even more preferably greater than 70%, most preferably greater than the product of 80% enantiomeric excess.
Non-mapping selective reaction changes chiral reagent (can be racemic or mapping is pure) into the product of a diastereomer enrichment.If chiral reagent is racemic, in the presence of chiral non-racemic body reagent or catalyzer, a kind of enantiomorph of reagent may react slowlyer than another.This class reaction is called as dynamic (dynamical) parsing, and wherein enantiomorph reagent decomposes by the differential speed of reaction, obtains the product of enantiomorph enrichment and the unreacted substrate of enantiomorph enrichment.
Dynamic (dynamical) parsing is usually by using enough reagent only to finish (reagent that is half mole of every mole of racemic substrate) with a kind of enantiomorph reagent react.The example that has been used for the catalyzed reaction of racemic reagent dynamic analysis comprises Sharpless epoxidation reaction and Noyori hydrogenation.
The zone selective reaction is wherein preferentially a reactive center but not the reaction that another reactive center inequality is carried out.For example, the regional selective reaction of the epoxide substrate of asymmetric replacement comprises the reaction on preferential in two epoxide ring carbon one.
Term " non-racemic " is used for chiral catalyst, and expression has greater than 50%, more preferably the Preparation of catalysts of at least 75% given enantiomorph.
" non-basically racemic " refers to have greater than 90% the Preparation of catalysts of the enantiomeric excess more preferably greater than 95% for the enantiomorph of given catalyzer.
Term " alkyl " refers to saturated aliphatic group, comprises straight chained alkyl, branched-chain alkyl, cycloalkyl (alicyclic), the cycloalkyl that alkyl replaces and the alkyl of cycloalkyl substituted.In preferred version, the straight or branched alkyl has 30 or still less (for example, straight chain is C at its main chain 1-C 30, side chain is C 3-C 30) carbon atom, the carbon atom more preferably less than 20.Similarly, preferred cycloalkyl has 4-10 carbon atom in its ring structure, more preferably have 5,6 or 7 carbon atoms in its ring structure.
Unless carbon atom number has explanation in addition, " low alkyl group " used in this application expression defines as above, has one to ten in its backbone structure, more preferably an alkyl to six carbon atom.Similarly, " low-grade alkenyl " has similar chain length with " low-grade alkynyl ".
Term " alkenyl " and " alkynyl " relate to similar length and the possible unsaturated aliphatic base that substitutes onto aforesaid alkyl, but wherein contain a two or triple carbon-to-carbon linkage respectively at least.
Term " organometallic compound " refers to comprise the compound of the atoms metal (as mercury, zinc, lead, magnesium or lithium) that is bonded directly to carbon atom or metalloid atom (as silicon, or tin), as methylmagnesium-bromide, and phenyl lithium, and phenyl-trimethylammonium-Xi.
Term " amine " and " amino " they are well known in the art, relate to amine unsubstituted and that replace, for example, and the group of can following general formula representing:
R wherein 9, R 10And R ' 10Represent the group that the valency rule is allowed independently of one another.
Abbreviation " DBU " refers to 1, and 8-diazabicyclo [5.4.0] 11 carbon-7-alkene have following structure:
Term " acyl amino " is well known in the art, refer to can following general formula group:
Figure A20061008248100483
R wherein 9Definition as above, R ' 11 expression hydrogen, alkyl, alkenyl or-(CH 2) m-R 8, wherein m and R 8Definition as above.
Term " amide group " is art-recognized, is the carbonyl that amino replaces, comprise can following general formula group:
R wherein 9, R 10Definition as above.Preferred acid amides does not comprise it may being unsettled imide.
Term " alkylthio " refers to have the definition alkyl as above of the sulphur of other connection.In preferred version, " alkylthio " group is represented one-S-alkyl ,-S-alkenyl ,-S-alkynyl and-S-(CH 2) m-R 8, wherein m and R 8Definition as above.Typical alkylthio comprises methylthio group, ethylmercapto group, etc.
Term " carbonyl " is well known in the art, comprise can following general formula group:
Wherein X is a key or expression oxygen or sulphur, and R 11Expression hydrogen, alkyl, alkenyl ,-(CH 2) m-R 8Or pharmacy acceptable salt, R ' 11Expression hydrogen, alkyl, alkenyl ,-(CH 2) m-R 8, wherein m and R 8Definition as above.
Wherein X is oxygen and R 11Or R ' 11When being not hydrogen, this formula is represented " ester ".
Wherein X is an oxygen, and R 11When defining as above, this group relates to carboxyl, and particularly when R11 was hydrogen, this formula was represented " carboxylic acid ".Wherein X is an oxygen, and R ' 11When being hydrogen, this formula is represented " manthanoate ".In general, when the Sauerstoffatom of following formula was substituted by sulphur, this formula was represented " thiocarbonyl ".
Wherein X is sulphur and R11 or R ' 11When being not hydrogen, this formula is represented " monothioester ".Wherein X is sulphur and R 11When being hydrogen, this formula is represented " thiocarboxylic acid ".Wherein X is sulphur and R ' 11When being hydrogen, this formula is represented " thiocarboxylic ".On the other hand, wherein X is a key and R 11When being not hydrogen, above-mentioned formula is represented " ketone " base.Wherein X is a key and R 11When being hydrogen, above-mentioned formula is represented " aldehyde " base.
Term used in this application " alkoxyl group " refers to have the definition alkyl as above of connected oxyradical.Typical alkoxyl group comprises methoxyl group, oxyethyl group, propoxy-, tert.-butoxy etc." ether " is two hydrocarbon that are connected with covalent linkage with oxygen.Correspondingly, the alkyl substituent on the ether alkyl is or similar in appearance to alkoxyl group, as being expressed as-the O-alkyl-O-alkenyl ,-O-alkynyl ,-O-(CH 2) m-R 8, wherein m and R 8Definition as above.
Term " sulphonate " is well known in the art, comprise can following general formula group:
R wherein 41Be electron pair, hydrogen, alkyl, cycloalkyl, or aryl.
Term triflyl, tosyl, mesyl and nonaflyl are well known in the art, relate separately to trifyl, p-tosyl group, methyl sulfo group, and nine fluorine fourth alkylsulfonyls.Term and triflate, tosylate mesylate and nonaflate are well known in the art, relate separately to triflate, p-tosylate, methanesulfonates and nine fluorine fourth sulfonate functionality and the molecule that contains this group.
Abbreviation Me, Et, Ph, Tf, Nf, Ts, Ms represent methyl respectively, ethyl, phenyl, trifyl, nine fluorine fourth alkylsulfonyls, p-tosyl group and methylsulfonyl.The more detailed table look-up of the abbreviation that organic chemistry filed is often used was delivered on the first phase of each volume on the Journal of Organic Chemistry; This table generally is present in the table that is called Standard List ofAbbreviations.List in the abbreviation of this table, and the abbreviation used of organic chemistry filed those of ordinary skill is enrolled at this and is enrolled as a reference.
Term " sulfoamido " is well known in the art, comprise can following general formula group:
Figure A20061008248100501
Term " sulfamyl " is well known in the art, comprise can following general formula group:
Figure A20061008248100502
Term used in this application " alkylsulfonyl " refer to can following general formula group:
Figure A20061008248100503
R wherein 44Be selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic radical, aryl, or heteroaryl.
Term used in this application " sulfoxide group " refer to can following general formula group:
R wherein 44Be selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic radical, aralkyl, or aryl.
Term used in this application " sulfuric ester " expression connects two hydroxyls or alkoxyl group definition alkylsulfonyl as above.In preferred version, sulfuric ester has following structure:
Figure A20061008248100511
R wherein 40And R 41There are not or independently for hydrogen alkyl, or aryl.In addition, R 40And R 41Form 5 to 10 ring structures altogether with alkylsulfonyl and connected Sauerstoffatom.
Similarly replacement can be resulted from alkenyl and alkynyl, for example obtains alkenyl amine, alkynylamine, alkenyl acid amides, alkynyl acid amides, the alkenyl imines, the alkynyl imines, sulfo-alkenyl, sulfo-alkynyl, the alkenyl of carbonyl substituted or alkynyl, alkenyloxy, alkynyloxy group, the alkynyl that alkenyl that metal replaces and metal replace.
Term used in this application " aryl " comprises may comprise zero to four heteroatomic 4-, 5-, and 6-and 7-unit monocyclic aryl, for example, and benzene, the pyrroles, furans, thiophene, imidazoles, the  azoles, thiazole, triazole, pyrazoles, pyridine, pyrazine, pyridazine and pyrimidine, etc.Have heteroatomic aryl in those ring structures and also can be described as " fragrant heterocycle ".One or more positions of aromatic ring can be replaced by aforesaid substituting group, for example, and halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro; mercaptan amine, imines, acid amides, phosphonic acid ester, phosphine, carbonyl, carboxyl, silyl; ether, thioether, alkylsulfonyl, seleno ether, ketone, aldehyde, ester, or-(CH 2) m-R 7,-CF 3,-CN, etc.
Term " heterocycle " or " heterocyclic radical " relate to wherein, and ring structure comprises one to four heteroatomic 4 to 10-unit, more preferably 5 to 7 ring structures.Heterocyclic radical comprises Pyrrolidine, oxolane, thiolane, imidazoles,  azoles, piperidines, piperazine, morpholine.The one or more positions of heterocyclic can be replaced by aforesaid substituting group, for example, and halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro; mercaptan amine, imines, acid amides, phosphonic acid ester, phosphine, carbonyl, carboxyl, silyl; ether, thioether, alkylsulfonyl, seleno ether, ketone, aldehyde, ester, or-(CH 2) m-R 7,-CF 3,-CN, etc.
Term " many ring " or " many cyclic groups " relate to wherein two or more carbon be two in abutting connection with the common two or more rings (for example, cycloalkyl, cycloalkenyl group, cycloalkynyl radical, aryl and/or heterocycle) of ring, for example this encircles and is " condensed ring ".The ring that connects by non-conterminous atom is called as " bridge " ring.Each ring of polycyclic can be replaced by aforesaid substituting group, for example, and halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro; mercaptan amine, imines, acid amides, phosphonic acid ester, phosphine, carbonyl, carboxyl, silyl; ether, thioether, alkylsulfonyl, seleno ether, ketone, aldehyde, ester, or-(CH 2) m-R 7,-CF 3,-CN, etc.
Any atoms of elements beyond term used in this application " heteroatoms " expression de-carbon or the hydrogen.Preferred heteroatoms is nitrogen, oxygen, sulphur, phosphorus and selenium.
In order to implement the present invention, chemical element is according to the Periodic Table of theElements, CAS version, and Handbook of Chemistry and Physics, 67thEd., 1986-87, inside cover determines.
The term ortho position, a position and contraposition are applicable to 1 respectively, 2-, 1,3-and 1, the dibasic benzene of 4-.For example, title 1,2-dimethylbenzene and o-Xylol are synonyms.
Term triflyl, tosyl, mesyl and nonaflyl are well known in the art, relate separately to trifyl, p-tosyl group, methyl sulfo group, and nine fluorine fourth alkylsulfonyls.Term and triflate, tosylate mesylate and nonaflate are well known in the art, relate separately to triflate, p-tosylate, methanesulfonates and nine fluorine fourth sulfonate functionality and the molecule that contains this group.
Abbreviation Me, Et, Ph, Tf, Nf, Ts and Ms represent methyl respectively, ethyl, phenyl, trifyl, nine fluorine fourth alkylsulfonyls, p-tosyl group and methylsulfonyl.The more detailed table look-up of the abbreviation that this area organic chemist often uses was delivered on the first phase of each volume on the Journal of Organic Chemistry; This table generally is present in the table that is called Standard List ofAbbreviations.List in the abbreviation of this table, and the abbreviation that organic field those of ordinary skill uses is enrolled as a reference at this.
The functional group of phrase used in this application " protecting group " expression protection potential reaction does not produce the temporary transient substituting group of undesirable chemical transformation.
The example of such protecting group comprises carboxylicesters, the silyl ether of alcohol and the acetal and the ketal of aldehyde and ketone.The existing summary of protecting group chemical field (Greene, T.W.; Wuts, P.G.M.Protective Groups in Organic Synthesis, 2nd ed.; Wiley:New York, 1991).
Term used in this application " replacement " expection includes all admissible substituting groups of organic compounds.Aspect widely, admissible substituting group includes the acyclic and cyclic of organic compounds, side chain with unbranched, isocyclic and heterocyclic, fragrance with nonaromatic substituting group.Typical substituting group comprises, for example, and at disclosed substituting group above.For suitable organic compound, admissible substituting group can be one or more and identical or different.For purposes of the invention, heteroatoms such as nitrogen can have the hydrogen substituting group and/or satisfy the disclosed organic compound substituting group of the valent any admissible the application of heteroatoms.The present invention does not plan to be limited to by any way the admissible substituting group of organic compound.
The inventive method
In some concrete scheme, the inventive method is expressed as flow process 1
Flow process 1
Wherein
X represents iodine, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly; Catalyzer comprises copper atom or ion, and ligand;
Alkali is represented brnsted base;
R represents alkyl, cycloalkyl, aralkyl, aryl, heteroaryl, formyl radical, acyl group, alkyl O 2C-, aryl O 2C-, heteroaryl O 2C-, aralkyl O 2C-, heteroaralkyl O 2C, acyl group (R ') N-, alkyl OC (O) N (R ')-, aryl OC (O) N (R ')-, aralkyl OC (O) N (R ')-, heteroaralkyl OC (O) N (R ')-,-N=C (alkyl) 2, or-N=C (aryl) 2
R ' expression H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, heteroaryl, formyl radical, acyl group, amino, or-C (NR ") N (R ") 2
R " represent H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl respectively independently;
R and R ' can represent=C (alkyl) 2 altogether, or=C (aryl) 2; And
R is connected by a covalent linkage with R ' non-imposedly;
Condition is when R is aryl or heteroaryl, and R ' is not formyl radical or acyl group;
Other condition is when R is formyl radical or acyl group, and R ' is not aryl or acyl group.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein X represents iodine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein X represents Br.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein X represents Cl.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, 1, the 2-diamines, 1,2-amino alcohol, 1,2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 6-xylenol, 2-isopropyl-phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1, the 2-diaminoethanes, 1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is a chelating ligand.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, wherein the ligand that comprises of catalyzer be replace non-imposedly 1, colamine, 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine by flow process 1 and the definition followed.
In some concrete scheme, the inventive method represents that wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide by flow process 1 and the definition followed.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 150 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 140 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 110 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 100 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 90 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 50 ℃.
In some concrete scheme, the inventive method represented by flow process 1 and the definition followed, and wherein this method temperature of carrying out is less than about 40 ℃.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein this method is carried out at ambient temperature.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein Z represents the aryl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein Z represents the phenyl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 1 and follows, wherein R represents H, or alkyl.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents 1; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1, colamine, 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents Br; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 1 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 1 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method is expressed as flow process 2
Wherein
X represents iodine, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly; (N-heteroaryl)-H represents the pyrazoles that replaces, pyrroles, tetrazolium, imidazoles non-imposedly; indazole, 1,2,3-triazoles; 1,2,4-triazole, indole carbazole; benzotriazole, benzoglyoxaline, guanine, purine; VITAMIN B4, xanthine, 8-azaadenine, 8-azo A Piao xanthine; uridylic, 6-azauracil, cytosine(Cyt), thymus pyrimidine; the 6-azathymine, uric acid, benzoylene urea, 4 (3H)-pyrimidones; pyridone, 1 (2H)-2 ketone, 1; 2,3-phentriazine-4 (3H)-ketone, 2-benzoxazol quinoline ketone, thymidine; uridine, (-)-inosine 1H-1,2,3,5-diazadiphosphole, 1H-1,2,3-azadiphosphole, 1H-1,2,4-azadiphosphole, 1H-1,2,4-diazaphosphole, 1H-1,2,3-diazaphosphole, 1H-1,3,2-diazaphosphole, 1H-1,2-azadiphosphole, 1H-1,3-azadiphosphole, 1H-1,2,3,4-triazaphosphole, 1H-1,2,3,5-dithiadiazolidene, 1H-1,3,2,4-dithiadiazolidene, 1,3,2-oxa-thiazole, 3H-1,3,2-oxa-thiazole, 1,3, the 2-dithiazole, 1H-1,2-azaborole, pentazole, 3H-1,2,3-two  azoles, 2H-1,2,3-oxa-diazine, 2H-1,2,4-oxa-diazine, 2H-1,2,5-oxa-diazine, 2H-1,2,6-oxa-diazine, 2H-1,2,3-thiadiazine, 2H-1,2,4-thiadiazine, 2H-1,2,5-thiadiazine, 2H-1,2,6-thiadiazine, 2H-1,2-thiazine, 1,3,5,2,4,6-three thia triazines, 2H-1,2,4,5-oxa-triazine, 4H-1,3,2,4-dithia diazine, 2H, 4H-1,3,2,5-two oxa-diazines, 2H-1,5,2,4-two oxa-diazines, 2H-1,2,4,6-thia triazine, 2H-1,2,4,5-thia triazine, 4H-1,3,2-dithiazine alkane, 4H-1,3,2-two  piperazines, 2H-1,5,2-two  piperazines, 1,3,4-dithiazine alkane, 4H-1,3, the 2-oxa-thiazine, 2H, 4H-1,5,2-oxa-thiazine, 2H-1,2-diaza , 2H-1,3-diaza , 2H-1,4-diaza , 2H-1,2,5-three azepine , 2H-1,3,5-three azepine , 2H-1,2,4-three azepine  1H-azepine , 2H-1,2,3,5-four azepine , 2H-1,2,4,6-four azepine , 2H-1,2,4,5-four azepine , 2H-1,5,2,4-dithia diaza , 1,3,5,2,4,7-three thias three azepine , 1,3,5,2,4-three thia diaza , pentahydro--1,3,5,2,4,6,8-three thias four bifurcations are hot because of, 2H, 6H-1,5,2,4,6,8-dithia four bifurcations hot because of, 2H-1,2,5-oxa-two bifurcations hot because of, 2H-1,2,6-oxa-two bifurcations are hot because of, 2H-1, and 2-oxa-bifurcation is hot because of, 2H-1,2-thia bifurcation hot because of, 4H-1,2,5-thia two bifurcations hot because of, 2H-1,2,6-thia two bifurcations hot because of, 5H-[1,2,4]-thiadiazoles [1,5-b] [1 also, 2,4] oxa-thiazole, triazolothiadiazole, thienothiadiazole 1H-imidazo [1,2-a] imidazoles, 4 H-furans [3,2-b] pyrroles [3,4-b], 1H-pyrrolo-pyrazoles, 1H-[2,3-d] the thieno-pyrazoles, 1H-[2,4-d] the thieno-pyrazoles, 1H-[2,3-c] the thieno-pyrazoles, 1H-[3,4-c] the thieno-pyrazoles, 1H-1,3-benzazaphole, 1The H-benzazepine, the 2H-2-benzazepine, 1H-1, the 3-benzodiazepine, 1H-1, the 4-benzodiazepine, 1H-1, the 5-benzodiazepine, 1H-1,2,4-benzo three azepine , 1H-1,2,5-benzo three azepine , 1H-1,3,4-benzo three azepine , or 3H-3-benzazepine;
Catalyzer comprises copper atom or ion, and ligand; And
Alkali is represented brnsted base.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein (N-heteroaryl)-H represents the pyrroles that replaces, pyrazoles, indoles, indazole, azaindole, carbazole, imidazoles, purine, or benzoglyoxaline non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 2 and follows, wherein X represents iodine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 2 and follows, wherein X represents bromine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 2 and follows, wherein X represents chlorine.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, 1, the 2-diamines, 1,2-amino alcohol, 1,2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 6-xylenol, 2-diisopropyl phenol, 1-naphthols, oxine, the 8-quinolylamine, DBU, 2-(aminomethyl) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(aminomethyl) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is a chelating ligand.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine by flow process 2 and the definition followed.
In some concrete scheme, the inventive method represents that wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide by flow process 2 and the definition followed.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 150 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 140 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 110 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 100 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 90 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 50 ℃.
In some concrete scheme, the inventive method represented by flow process 2 and the definition followed, and wherein this method temperature of carrying out is less than about 40 ℃.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein this method is carried out at ambient temperature.
In some concrete scheme, the definition that the inventive method is expressed as flow process 2 and follows, wherein Z represents the aryl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 2 and follows, wherein Z represents the phenyl that replaces non-imposedly.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(aminomethyl) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(aminomethyl) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represented by flow process 2 and the definition followed, and wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 6-xylenol, 2-diisopropyl phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(aminomethyl) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(aminomethyl) glycine, N, N, N ', N '-tetramethyl--1, the 2-diaminoethanes, 1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal fluoride, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1, the amino alkane of 2-; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(aminomethyl) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(aminomethyl) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents Br; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(aminomethyl) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(aminomethyl) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-dibromopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-dichloro propylphenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is to replace 1 non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, 2 hydroxy ethylamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 2 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 2 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 2 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, c i s-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method is represented by flow process 3:
Figure A20061008248100811
Flow process 3
Wherein
X represents iodine, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly; Catalyzer comprises copper atom or ion, and ligand;
Alkali is represented brnsted base; And
R represents the alkyl that replaces, cycloalkyl, aralkyl, heteroaralkyl, alkenyl alkyl, or alkynyl alkyl non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 3 and follows, wherein X represents iodine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 3 and follows, wherein X represents bromine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 3 and follows, wherein X represents chlorine.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, 1, the 2-diamines, 1,2-amino alcohol, 1,2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represented by flow process 31 and the definition followed, and wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 6-xylenol, 2-isopropyl-phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1, the 2-diaminoethanes, 1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is a chelating ligand.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine by flow process 3 and the definition followed.
In some concrete scheme, the inventive method represents that wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide by flow process 3 and the definition followed.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein catalyzer is less than or equal to about 5 mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 150 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 140 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 110 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 100 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 90 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 50 ℃.
In some concrete scheme, the inventive method represented by flow process 3 and the definition followed, and wherein this method temperature of carrying out is less than about 40 ℃.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein this method is carried out at ambient temperature.
In some concrete scheme, the definition that the inventive method is expressed as flow process 3 and follows, wherein Z represents the aryl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 3 and follows, wherein Z represents the phenyl that replaces non-imposedly.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1, the amino alkane of 2-; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 3 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1,2-diaminoethanes-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7 dimethyl-1, the 10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture thanomin of 2-diamino-cyclohexane, 1, the 2-diaminoethanes, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 3 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, and 2,6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is to replace 1 non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, 2 hydroxy ethylamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N ' dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents Cl; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 3 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 3 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method is expressed as flow process 4:
Figure A20061008248100951
Flow process 4
Wherein
X represents iodine, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly;
L represents hydrogen or negative charge;
Catalyzer comprises copper atom or ion, and ligand;
Alkali is represented brnsted base;
R represents hydrogen, the alkyl that replaces, cycloalkyl, aralkyl, aryl, or heteroaryl non-imposedly;
R ' represents hydrogen, alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl, formyl radical, acyl group ,-CO respectively independently 2R " ,-C (O) N (R) 2, alkylsulfonyl ,-P (O) (OR ") 2,-CN, or-NO 2
R " represent non-imposed ground substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl respectively independently; And
C (R ') 2(R) can represent nitrile altogether.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein X represents iodine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein X represents bromine.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein X represents chlorine.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, 1, the 2-diamines, 1,2-amino alcohol, 1,2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 6-xylenol, 2-diisopropyl phenol, 1-naphthols, oxine, the 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is a chelating ligand.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine by flow process 4 and the definition followed.
In some concrete scheme, the inventive method represents that wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide by flow process 4 and the definition followed.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 150 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 140 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 110 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 100 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 90 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 50 ℃.
In some concrete scheme, the inventive method represented by flow process 4 and the definition followed, and wherein this method temperature of carrying out is less than about 40 ℃.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein this method is carried out at ambient temperature.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein Z represents the aryl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein Z represents the phenyl that replaces non-imposedly.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein R represents hydrogen.
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein R represents to represent independently respectively acyl group, or-CO 2R ".
In some concrete scheme, the definition that the inventive method is expressed as flow process 4 and follows, wherein R represents to represent independently respectively alkyl, cycloalkyl, or aralkyl.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, 1,2-diamino-cyclohexane 1,10-phenanthroline, 2-hydroxyethyl amine, or 1; And this alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 4 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,4-diamino-cyclohexane, anti--1, the 4-diamino-cyclohexane, cis-and anti--1, the mixture of 4-diamino-cyclohexane, cis-N, N '-dimethyl-1,4-diamino-cyclohexane, instead-and N, N '-dimethyl-1,4-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 4-diamino-cyclohexane, or N, N '-dimethyl-1,4-diaminoethanes; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 4 represents that wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the virtue 1 that replaces non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; The ligand that catalyzer comprises is to replace 1 non-imposedly, 2-diamino-cyclohexane, 1,10-phenanthroline, 2 hydroxy ethylamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 4 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the definition that the inventive method is followed by flow process 4 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; Alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, the carbene imidazolium salts, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, method of the present invention represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2, and 6-xylenol, 2-diisopropyl phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicylic amide, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5-methyl isophthalic acid, the 10-phenanthroline, 5-chloro-1,10-phenanthroline,, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine, and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the definition that the inventive method is followed by flow process 4 represents that wherein X represents chlorine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; Alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
In some concrete scheme, the inventive method represents that by flow process 4 and the definition followed wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
Catalyzer of the present invention
In general, the catalyzer that is used for the inventive method comprises a copper atom or ion and a ligand.The copper atom of catalyzer or ion can be any mantoquitas that can buy from the market, for example, and copper (I) or copper (II) salt.In some concrete scheme, copper atom or ion provide as copper (I) iodide form.
The ligand of catalyzer comprises Lewis alkalescence atom, for example, is selected from nitrogen, oxygen, sulphur, phosphorus, and arsenic, so Lewis alkalescence atom can with above-mentioned copper atom or ionic interaction.The ligand of catalyzer can be a chelating ligand,, comprises two Lewis alkalescence atoms that have spatial relation each other that is, for example, be selected from nitrogen, oxygen, the ligand of phosphorus and arsenic, so Lewis alkalescence atom can while and above-mentioned copper atom or ionic interaction.For example, chelating ligand can be a diamines, amino alcohol, or two phosphine.In some concrete scheme, chelating ligand is 1, the 2-diamines, or 1, the 3-diamines.In some concrete scheme, chelating ligand is 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or diaminoethanes.In some concrete scheme, chelating ligand is 1,2-diamino-cyclohexane, N, N '-dimethyl-1,2-diamino-cyclohexane, N-tolyl-1,2-diamino-cyclohexane, 1,10-phenanthroline, thanomin, 1, or N, N '-dimethyl-1.In some concrete scheme, chelating ligand is cis-1, and the 2-diamino-cyclohexane is anti--1,2-diamino-cyclohexane, or cis-and anti--1, the mixture of 2-diamino-cyclohexane.In addition, for asymmetric chelating ligand, ligand can be used as single enantiomorph, the mixture of steric isomer, or the form of racemic mixture provides.In some concrete scheme, ligand is as the solvent of the inventive method.For example, the ligand that comprises of catalyzer is in the concrete scheme for the amine of liquid under the inventive method implementation condition therein, and this method can use this amine to implement as solvent.
The copper atom of the inventive method catalyzer or ion and ligand can be respectively or side by side are added in the reaction mixture, and perhaps the form of the title complex that they can preformed catalyst adds.Although the inventive method does not need to form copper-chelating ligand title complex, such title complex may exist.And, the various features of properties influence the inventive method of this ligand.
In some concrete scheme, the catalyzer of the inventive method is with the form and the carrier of covalent linkage, and for example, polymer beads or resin connect.For example, catalyzer of the present invention can covalent linkage form and carrier, for example, Wang resin connects.In addition, form and carrier that one or more substrates of the inventive method can covalent linkage, for example, polymer beads or resin connect.For example, form and carrier that the Z-X substrate of the inventive method can covalent linkage, for example, Wang resin connects.Optionally, the nucleophilic substrate is promptly effectively replaced form and carrier that the substrate of the X among the Z-X can covalent linkage in the inventive method, and for example, Wang resin connects.In addition, in some concrete scheme, the form that two substrates can covalent linkage is connected with carrier.In some concrete scheme, one or more substrates or catalyzer or in them some are with semi-permeable membranes, for example, and the isolated in form of dialysis bag.
Suitable alkali
The inventive method can be used various brnsted bases.Usually, the inventive method can be used any brnsted base.For example, suitable alkali comprises K 3PO 4, K 2CO 3, Na 2CO 3, Tl 2CO 3, Cs 2CO 3, K (OtBu), Li (OtBu), Na (OtBu), K (OPh), and Na (OPh), or its mixture.In some concrete scheme, the brnsted base of use can be selected from phosphoric acid salt, carbonate, and alkoxide.In some concrete scheme, alkali can be selected from potassiumphosphate, salt of wormwood, cesium carbonate, and sodium tert-butoxide.
Usually, the inventive method needn't be used excessive greatly alkali.In some concrete scheme,, use to be no more than four normal alkali with respect to nucleophilic reagent.In other concrete schemes,, use to be no more than two normal alkali with respect to nucleophilic reagent.In addition, replace in the reaction of its conjugate base, may not need other alkali at the negatively charged ion that uses corresponding nucleophilic reagent.
Nucleophilic reagent
The nucleophilic reagent that is used for the inventive method can be by experienced technician according to some Standard Selection.In general, suitable nucleophilic reagent has one or more following character: 1) its close electric position and substrate reactions that can require; 2) it will with the reaction of substrate in obtain useful product; 3) it can be in the functional group outside the close electric position that requires and substrate reactions; 4) it will be to catalyst mechanism and the substrate reactions of small part by chiral catalyst; 5) with after substrate carries out the reaction of requirement, it can not produce undesirable other reaction basically; And 6) it basically not can with catalyst reaction or decomposition catalyst.Obviously, although may there be bad side reaction (as catalyst degradation), the speed of such reaction can be slowed down--by selective reagents and condition--with the speed ratio of the reaction that requires.
The preferred nucleophilic reagent of measuring given transformation can use routine test.For example, if in order to obtain carbon-nitrogen bond, what need contains nitrogen nucleophile and can be selected from amine, acid amides, and imide.In addition, heteroaryl also can be used as nucleophilic reagent.
For example, the carbon-nitrogen bond that can form comprises the indoles that replaces non-imposedly, pyrroles, or carbazole.And, much other nitrogen-containing functional group in forming the method for carbonnitrogen bond as substrate.For example, the suitable substrate of carbon-nitrogen bond formation method of the present invention is a hydrazine, hydrazides, hydrazone, imines and carbalkoxy hydrazine.
Similarly, oxygen containing nucleophilic reagent, as alcohol, alkoxide, or siloxanes can be used to form oxygen-carbon bond; And the nucleophilic reagent of sulfur-bearing, as mercaptan, can be used to obtain carbon-sulfide linkage.Similarly, carbon nucleophile, for example, malonic ester or beta-ketoester can be used to obtain C-C.Other suitable nucleophilic reagents may be conspicuous for the organic chemistry filed those of ordinary skill.The nucleophilic reagent that is introduced into reaction mixture as negatively charged ion may comprise conventional counterion, for example, and alkali metal cation, alkaline earth metal cation, or ammonium ion.In some concrete scheme, nucleophilic group can be the part of substrate, causes forming the reaction of intramolecular bond.
In some concrete scheme, nucleophilic reagent is selected from primary amide, secondary amide, and lactan, hydrazine, imines, hydrazone, carbazic acid salt, primary amine, secondary amine contains NH heteroaryl (for example, pyrroles, indoles, and imidazoles), malonic ester, carbamate, imide, and alcohol.
Aryl, heteroaryl or vinyl halide or sulphonate
The inventive method can be used to obtain fragrant halocarbon sulphonate, heteroaryl halogenide or sulphonate, or the halogen that is connected with carbon atom or the sulphonate of vinyl halide or sulphonate, and the nucleophilic nitrogen of second molecule or carbon or Sauerstoffatom.Certainly, as mentioned above, fragrant halocarbon, heteroaryl halogenide, or the halogen that is connected with carbon of vinyl halide, or aromatic yl sulphonate, heteroaryl sulfonates, or the sulphonate that is connected with carbon of vinyl sulfonate, and nucleophilic nitrogen or carbon can be the part of single molecule, is used for the formation of intramolecular bond.
In some concrete scheme, use wherein aromatic yl group as aromatic hydrocarbon (monocycle or many rings), as benzene, naphthalene, anthracene and luxuriant and rich with fragrance fragrant halocarbon or sulphonate.In some concrete scheme, aryl halide can be selected from the phenyl halogenide that replaces non-imposedly.
In some concrete scheme, heteroaryl halogenide that uses or the heteroaryl groups in the sulphonate be as heteroaryl (monocycle or many ring), as the pyrroles, and thiophene, thianthrene, furans, pyrans, isobenzofuran, chromene, xanthene, phenoxathiin, pyrroles, imidazoles, pyrazoles, thiazole, isothiazole, different  azoles, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indoles, indazole, purine, quinolizine, isoquinoline 99.9, quinoline, phthalazines, naphthyridines, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridines, acridine, perimidine, phenanthroline, azophenlyene, phenarsazine, thiodiphenylamine, furan are certainly, fen  piperazine, Pyrrolidine, oxolane, thiolane, the  azoles, piperidines, piperazine, morpholine.
In general, suitable aromatic substance has chemical formula ZpArX, and wherein Ar is aryl or heteroaryl; And X is sulphonate or is selected from chlorine, the halogen of bromine and iodine.In some concrete scheme, X is for being selected from chlorine, the halogen of carbonate and iodine.In some concrete scheme, X represents sulfonate ester group.In addition, Z represents selectable substituting group on one or more aromatic rings, although each Z (p＞1) is independent the selection.Only for instance, allow as valency and stability, each independently replace can for, halogen, low alkyl group, low-grade alkenyl; low-grade alkynyl, carbonyl (for example, ester, carboxylicesters, or manthanoate), thiocarbonyl is (for example; monothioester, carbothioic acid ester, or thiocarboxylic), aldehyde, amino, acyl amino; amide group, amidino groups, cyano group, nitro, azido-; alkylsulfonyl, sulfoxide group, sulfuric ester, sulphonate, sulphonamide; sulfoamido, phosphoryl, phosphonic acid ester, phosphinate ,-(CH 2) m-R 8,-(CH 2) m-OH ,-(CH 2) m-O-low alkyl group ,-(CH 2) m-O-low-grade alkenyl ,-(CH 2) m-O-(CH 2) n-R g,-(CH 2) m-SH ,-(CH 2) m-S-low alkyl group ,-(CH 2) m-S-low-grade alkenyl ,-(CH 2) m-S-(CH 2) n-R 8, or the protecting group of above-mentioned group or solid or polymer support; R 8Expression replaces or unsubstituted aryl, aralkyl, cycloalkyl, cycloalkenyl group, or heterocycle; And n and m are respectively zero or 1 to 6 integer independently.When aryl was phenyl, the scope of p was 0 to 5.For condensed ring, aryl the number at replacement position greater than five, the range of definition of p must suitably be regulated.
Reaction conditions
The inventive method can be carried out under very wide condition, although solvent and temperature range that obvious the application states are not restrictive, only is equivalent to the preferred mode of the inventive method.
In general, mild conditions is used in the reaction of hope, can influence reagent, catalyzer, or product sharply.For example, reaction temperatures affect speed of response, and reagent, the stability of product and catalyzer.
In some concrete scheme, the temperature that the inventive method is carried out is less than about 150 ℃.In some concrete scheme, the temperature that the inventive method is carried out is less than about 140 ℃.In some concrete scheme, the temperature that the inventive method is carried out is less than about 110 ℃.
In some concrete scheme, the temperature that the inventive method is carried out is less than about 100 ℃.In some concrete scheme, the temperature that the inventive method is carried out is less than about 90 ℃.In some concrete scheme, the temperature that the inventive method is carried out is less than about 50 ℃.In some concrete scheme, the temperature that the inventive method is carried out is less than about 40 ℃.In some concrete scheme, the inventive method is carried out at ambient temperature.
In general, this is reflected in the liquid reaction medium and carries out.This reaction can be carried out under the situation that does not add solvent.Optionally, this reaction can be carried out in inert solvent, and preferably one of them reactive component comprises that catalyzer is essentially dissolved.Suitable solvent comprises ether such as ether, 1, and 2-glycol dimethyl ether, diglyme, t-butyl methyl ether, tetrahydrofuran (THF) etc.; Halide solvent such as chloroform, methylene dichloride, ethylene dichloride, chlorobenzene, etc.; Aliphatic series or aromatic hydrocarbon solvent such as benzene, dimethylbenzene, toluene, hexane, pentane etc.; Ester and ketone such as ethyl acetate, acetone, and 2-butanone; Polar protic inert solvent such as acetonitrile, methyl-sulphoxide, dimethyl formamide etc.; The combination of two or more solvents.
The present invention also is expected at the biphase mixture of solvent, the reaction in emulsion or the suspension, or the reaction in lipid vesicle or bilayer.In some concrete scheme, preferred reagent is fixed on the catalyzed reaction in the solid phase on the carrier.
In some concrete scheme, preferably as the reaction under the inert gas atmosphere of nitrogen or argon.
Reaction process of the present invention can be successive, and semi-continuous or batch-wise mode is according to the recirculation operation that requires to comprise liquid.
The mode that the inventive method is preferably carried out in batches.Similarly, add reactive component, the mode of catalyzer and solvent or order neither be reacted successful key usually, can finish by the mode of any routine.
This reaction can be in the single reaction district or multi-reaction-area carry out, can carry out continuously or carry out simultaneously, also can in the series in elongated tubular area or such zone, carry out in batches or continuously.During reaction, the material of use should be to the raw material inert, and the manufacturing of equipment should be able to be stood the temperature and pressure of reaction.During reaction raw material is introduced the introducing of reaction zone in batches or continuously and/or regulated raw material or the mode of the amount of component can be the mode that is advantageously used in keeping the material molar ratio of needs.This reactions steps can be subjected to a former influence of expecting the increment of another raw material.Equally, this reactions steps can combine with the adding of raw material to metal catalyst.When finishing, conversion does not need or obtains, and raw material can separate from product, and recycle back enters reaction zone then.
This method can be carried out in the stainless or similar type reaction equipment at enamelled.Reaction zone can be equipped with one or more inside and/or external hot device with control over-drastic temperature fluctuation, or prevents " out of control " of any possible temperature of reaction.
In addition, one or more reagent or catalyzer can be by connecting or incorporating polymkeric substance into or other insoluble substance matrix is fixed.
Transformation subsequently
The inventive method synthetic can be the intermediate in the finished product or the synthesis flow.If the inventive method synthetic product is an intermediate, this product can carry out one or more additional transformations, obtains the final product that needs.The additional transformation of such expection comprises isomerization, hydrolysis, oxidation, reduction, alkylene, functional group's change are eliminated in addition, the reaction of transition metal medium, transition-metal catalysis, key forms reaction, scission reaction, fragmentation reaction, thermal response, photochmeical reaction, cycloaddition, sigmatropic rearrangement, electrocyclic reaction, chemical selective reaction, regional selective reaction, hindrance, non-mapping selective reaction, mapping selective reaction, and dynamic analysis.The present invention comprises the inventive method especially as known or new medicine, antiviral for example, and microbiotic and analgesic agent synthetic are initial, intermediary or final step.
The information storage of combination
The inventive method is easily supported screening of medicaments, agrochemicals or other biological or active substance or relate to the formation of information storage of the combination of compounds of material mass.The information storage of combination of the present invention is the chemically mixture of relevant compound that can screen the character that needs; This information storage can in the solution or with on the covalent linkage connection carrier.The preparation of many related compounds in single reaction reduced and simplified the number of the screening process that need carry out widely.Can pass through ordinary method suitable biology, medicine, agrochemicals or physical properties.
Diversity in the information storage can multiple different level produce.For example, the core aromatic yl group that is used for the substrate aromatic yl group of combined method can be different, for example different heterocycle structure, and/or its substituting group can change.
The various technology of this area all can be used for producing the combined information repository of organic molecule.Referring to, for example, Blondelle et al. (1995) Trends Anal.Chem.14:83; TheAffymax U.S. patent 5,359,115 and 5,362,899:the Ellman U.S. patent 5,288,514:the Still et al.PCT applies for WO94/08051; Chenetal. (1994) JACS 116:2661:Kerr et al. (1993) JACS 115:252; PCT applies for WO92/10092, WO93/09668 and WO91/07087; And theLerner et al.PCT application WO93/20242).Correspondingly, various comprise about 16 to 1,000,000 or more multiunit information storage can be synthesized and be used for the screening of sp act or character.
In exemplary concrete scheme, the unitary information storage that replaces can use the disclosed technology of Still et al.PCT application WO94/08051 that is suitable for, for example, the hydrolyzable or photolysis group of a position by being positioned at substrate is connected in polymer beads, the present invention react synthetic.According to the technology of Still et al., information storage synthesizes on one group of globule, and each globule comprises that is determined a unitary marker special on the globule.Be particularly suitable for finding that at one globule can be dispersed on the permeable membrane surface in the concrete scheme of enzyme inhibitors, and the cracking of unit by the globule tie point discharges from globule.Unit on each globule passes film and is diffused into the mensuration zone, and it will interact with zymophore at this place.
Embodiment
Embodiment
Generally disclose the present invention at present, may be more readily understood the present invention by reference following examples, the following example is just to explanation some aspect of the present invention and concrete scheme, do not plan to limit the present invention.
Embodiment 1
General method A--uses aryl or heteroaryl iodide arylation
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), acid amides (1.2 mmole) and K 3PO 4(2.1 mmole) finds time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%) dodecane (235 microlitre) aryl iodide (1.0 mmole) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate by dodging formula purification by chromatography resistates, obtains pure products.
Embodiment 2
General method B--uses aryl or heteroaryl iodide arylation
In the flame-dried Schlenk pipe that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), heterogeneous ring compound (1.2 mmole) and K 3PO 4(2.1 mmole) finds time twice and the filling argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) 5-iodo-m-xylene (144 microlitres, 1.0 mmoles), anti--1, the 2-cyclohexane diamine (12 microlitres, 0.10 mmole, 10mol%) and dioxane (1.0 milliliters).Heated 20 hours in 110 ℃ oil bath with the Schlenk seal of tube and with reaction mixture.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Concentrated filtrate by column chromatography purification gained resistates, obtains purified product.
Embodiment 3
General method C--uses aryl or heteroaryl bromide arylation
In the Schlenk pipe of drying that contains stirring rod that can seal again, pack into cuprous iodide (20 milligrams, 0.1 mmole, 10mol%), acid amides (1.2 mmole) and K 3PO 4(425 milligrams, 2 mmoles) find time and the filling argon gas.Injection is anti--1,2-diamino-cyclohexane (11.5 milligrams, 0.1 mmole), and heteroaryl bromide (1.0 mmole) and dioxane (1 milliliter), and under argon gas stream, with the alternative barrier film of tetrafluoroethylene nut.Seal this pipe, and with this mixture stirs and heating specifies in 110 ℃ oil bath time.With gained mixture cool to room temperature and by diatomite filtration, use the methylene dichloride wash-out.Concentrating under reduced pressure filtrate, resistates carries out silica gel column chromatography.
Embodiment 4
N-(4-allyloxycarbonyl phenyl) benzamide
Figure A20061008248101161
Use general method A, make benzamide (150 milligrams, 1.24 mmoles) and 4-iodo-benzoic acid allyl ester (300 milligrams, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 3: 1; 10 milliliters of flow points).Flow point 8-15 provides 266 milligrams of (91% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ8.14-8.09(m，2H)，8.00(brs，1H)，7.93-7.88(m，2H)，7.80-7.75(m，2H)，7.63-7.58(m，1H)，7.56-7.51(m，2H)，6.07(ddt，J＝17.2，11.7，5.6Hz，1H)，5.45(dq，J＝17.2，1.4Hz，1H)，5.32(dq，J＝11.7，1.4Hz，1H)，4.85(dt，J＝5.6，1.4Hz，2H).
Embodiment 5
N-benzyl-N-(3, the 5-3,5-dimethylphenyl) methane amide
Figure A20061008248101162
Use general method A, make N-benzyl methane amide (170 milligrams, 1.26 mmoles) and 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 7-13 provides 247 milligrams of oily products that (99% productive rate) is colourless.
1H NMR(400MHz，CDCl 3)：δ8.55(s，1H)，7.39-7.22(m，5H)，6.91(s，1H)，6.75(s，2H)，5.00(s，2H)，2.30(s，6H).
Embodiment 6
N-(2-dimethylaminophenyl) benzamide
Figure A20061008248101171
Use general method A, make benzamide (150 milligrams, 1.24 mmoles) and N, N-dimethyl-2-Iodoaniline (160 microlitres, 1.05 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 7: 1; 15 milliliters of flow points).Flow point 8-15 provides 239 milligrams of (95% productive rate) light yellow oily products.
1H NMR(400MHz，CDCl 3)：δ9.42(br s，1H)，8.57(dd，J＝7.8，1.4Hz，1H)，7.98-7.92(m，2H)，7.62-7.51(m，3H)，7.26(dd，J＝7.8，1.4Hz，1H)，7.22(td，J＝7.8，1.4Hz，1H)，7.12(td，J＝7.8，1.4Hz，1H)，2.74(s，6H).
Embodiment 7
N-(2-nitrophenyl) benzamide
Use general method A, make benzamide (150 milligrams, 1.24 mmoles) and 1-iodo-2-oil of mirbane (260 milligrams, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 8: 1; 15 milliliters of flow points).Flow point 8-14 provides 177 milligrams of (70% productive rate) light yellow needle-like products. 1Reports such as HNMR spectrum and Murphy consistent.Murphy，J.A.；Rasheed，F.；Gastaldi，S.；Ravishanker，T.；Lewis，N.J.Chem.Soc.，Perkin Trans 1 1997，1549.
Embodiment 8
N-(4-aminophenyl)-N-phenylacetamide
Figure A20061008248101173
Use general method A, make Acetanilide (165 milligrams, 1.22 mmoles) and 4-Iodoaniline (228 milligrams, 1.04 mmoles) combination.Thick product dodges (2 * 20 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 1: 4; 20 milliliters of flow points).Flow point 10-20 provides 192 milligrams of (82% productive rate) light yellow solid shape products.[93 pages of Fig. 4 of original text]
1H NMR(400MHz，CDCl 3)：δ7.50-7.10(m，5H)，7.09-7.04(m，2H)，6.74-6.61(m，2H)，3.90-3.50(br s，2H)，2.07(s，3H).
Embodiment 9
4-amino-N-(3, the 5-diamino-phenyl) benzamide
Figure A20061008248101181
Use general method A, make 4-aminobenzamide (170 milligrams, 1.25 mmoles) and 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 20 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).
Flow point 9-18 provides 246 milligrams of (98% productive rate) white solid products.
1H NMR(400MHz，CDCl 3)：δ7.74-7.69(m，2H)，7.66(brs，1H)，7.28(s，2H)，6.78(s，1H)，6.74-6.69(m，2H)，4.05(br s，2H)，2.33(s，6H). 13C NMR(100MHz，CDCl 3)：δ165.7，150.3，139.1，138.6，129.2，126.2，124.8，118.2，114.6，21.8.
Embodiment 10
N-(4-benzylamino carbonyl phenyl)-N-methylformamide
Figure A20061008248101182
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), 4-iodo-N-benzyl benzamide (350 milligrams, 1.04 mmoles), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%), dodecane (235 microlitre), N-methylformamide (74 microlitres, 1.27 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Ethyl acetate-methylene dichloride 2: 1; 20 milliliters of flow points).Flow point 7-18 provides 273 milligrams of (98% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ8.57(s，1H)，7.90-7.86(m，2H)，7.40-7.29(m，5H)，7.25-7.20(m，2H)，6.62(br s，1H)，4.66(d，J＝5.7Hz，2H)，3.35(s，3H). 13C NMR (100MHz，CDCl 3)：δ166.6，162.3，145.2，138.4，132.2，129.2，129.0，128.3，128.1，121.5，44.6，32.0.
Embodiment 11
N-(3, the 5-3,5-dimethylphenyl)-2-azetidinone
Figure A20061008248101191
Use general method A, make 2-azetidinone (8 8 milligrams, 1.24 mmoles) and 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 1: 1; 15 milliliters of flow points).Flow point 5-10 provides 173 milligrams of (95% productive rate) white solid products.
1H NMR(400MHz，CDCl 3)：δ7.01(s，2H)，6.76(s，1H)，3.61(t，J＝4.5Hz，2H)，3.10(t，J＝4.5Hz，2H)，2.32(s，6H).
Embodiment 12
N-(2-thienyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%) and K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%), dodecane (235 microlitre), 2-iodothiophen (115 microlitres, 1.04 mmole), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 1; 20 milliliters of flow points).Flow point 9-15 provides 174 milligrams of (100% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ6.95(dd，J＝5.5，1.3Hz，1H)，6.90(dd，J＝5.5，3.7Hz，1H)，6.55(dd，J＝3.7，1.3Hz，1H)，3.92(t，J＝7.4Hz，2H)，2.66(t，J＝7.4Hz，2H)，2.27(p，J＝7.4Hz，2H). 13C NMR(100MHz，CDCl 3)：δ172.4，140.9，124.2，118.4，110.9，49.2，31.7，18.3.
Embodiment 13
Use the 0.2mol% cuprous iodide to prepare N-(4-methoxyphenyl)-N-methylformamide
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 0.2mol%) and K 3PO 4(2.25 grams, 10.6 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (33 microlitres, 0.269 mmole, 5.2mol%), dodecane (1.20 milliliters), 4-iodoanisole (1.22 grams, 5.21 mmole), N-methylformamide (360 microlitres, 6.15 mmoles) and dioxane (5.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 1.5 * 10cm silicagel pad, with 50 milliliters of eluent ethyl acetates.Concentrate light green filtrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 1; 20 milliliters of flow points).Flow point 8-17 provides 840 milligrams of oily products that (98% productive rate) is colourless. 1Reports such as H NMR spectrum and Hoffman consistent.Hoffman，R.V.；Salvador，J.M.J.Org.Chem.1992，57，4487.
Embodiment 14
40 ℃ of preparation N-(2-methoxyphenyl) benzamide
Figure A20061008248101211
Use general method A, benzamide (150 milligrams, 1.24 mmoles) and 2-iodoanisole (135 microlitres, 1.04 mmoles) were reacted 18 hours at 40 ℃.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 8-12 provides 49 milligrams of oily products that (21% productive rate) is colourless. 1Reports such as H NMR spectrum and Narasaka consistent.Tsutsi，H.；Ichikawa，T.；Narasaka，K.Bull.Chem.Soc.Jpn.1999，72，1869.
Embodiment 15
1-benzyl-2-(3, the 5-3,5-dimethylphenyl) hydrazine
Figure A20061008248101212
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), benzoyl hydrazine (170 milligrams, 1.25 mmoles), K 3PO 4(290 milligrams, 2.10 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%) dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 9-13 provides 159 milligrams of (64% productive rate) light tan solid state products.
1H NMR(300MHz，CDCl 3)：δ8.06(br s，1H)，7.87-7.82(m，2H)，7.60-7.44(m，3H)，6.58(s，1H)，6.54(s，2H)，6.32(brs，1H)，2.25(s，6H).
Embodiment 16
1-tertbutyloxycarbonyl-1-(4-phenyl) hydrazine
Figure A20061008248101221
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (50 milligrams, 0.263 mmole, 5.1mol%), 1, the 10-phenanthroline (100 milligrams, 0.555 mmole, 11mol%), 4-iodine biphenyl (1.45 gram, 5.18 mmoles), Cs 2CO 3(2.30 grams, 7.06 mmoles) find time and the filling argon gas.Under argon atmospher, add tertiary butyl carbazates (825 milligrams, 6.24 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 1 * 1cm silicagel pad, with 50 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 4: 1; 20 milliliters of flow points).Flow point 9-20 provides 1.29 gram (88% productive rate) faint yellow solid shape products.
1H NMR(400MHz，CDCl 3)：δ7.64-7.59(m，2H)，7.57(s，4H)，7.48-7.43(m，2H)，7.38-7.33(m，1H)，4.50(s，2H)，1.56(s，9H).
Embodiment 17
N-(3, the 5-3,5-dimethylphenyl) benzophenone imine
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), sodium tert-butoxide (150 milligrams, 1.56 mmoles) is found time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%), dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmole), benzophenone imine (210 microlitres, 1.25 mmoles) and dioxane (1.0 milliliters).Stirred 36 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 30: 1; 15 milliliters of flow points).Flow point 6-11 provides 46 milligrams of (15% productive rate) light tan solid state products.
1H NMR(300MHz，CDCl 3)：δ7.79-7.75(m，2H)，7.52-7.40(m，3H)，7.34-7.26(m，3H)，7.20-7.15(m，2H)，6.60(s，1H)，6.39(s，2H)2.19(s，6H).
Embodiment 18
N-(3, the 5-3,5-dimethylphenyl) Benzophenonehydrazones
Figure A20061008248101231
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), Benzophenonehydrazones (245 milligrams, 1.25 mmoles), sodium tert-butoxide (145 milligrams, 1.51 mmoles) is found time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%), dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 5: 1 wash-outs of 10 milliliters of hexane-ethyl acetate.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 40: 1; 15 milliliters of flow points).Flow point 10-12 provides 251 milligrams of (80% productive rate) golden yellow solid state products. 1Reports such as H NMR spectrum and Buchwald consistent.Wagaw，S.；Yang，B.H.；Buchwald，S.L.J.Am.Chem.Soc.1999，44，10251.
Embodiment 19
N-(3, the 5-3,5-dimethylphenyl)-N, the N-pentanoic
Figure A20061008248101241
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), pentanoic (210 milligrams, 1.24 mmoles), sodium tert-butoxide (145 milligrams, 1.51 mmoles) is found time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 11mol%), dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 24 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 5: 1 wash-outs of 10 milliliters of hexane-ethyl acetate.Concentrated filtrate dodges (2 * 25 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 40: 1; 15 milliliters of flow points).Flow point 9-13 provides 211 milligrams of (74% productive rate) white crystals shape products.
1Reports such as H NMR spectrum and Goodbrand consistent.Goodbrand，H.B.；Hu，N.X.J.Org.Chem.1999，64，670.
Embodiment 20
1-(3, the 5-3,5-dimethylphenyl) indazole
Figure A20061008248101242
Use general method A, make indazole (148 milligrams, 1.25 mmoles) and 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 10: 1; 10 milliliters of flow points).Flow point 4-10 provides 222 milligrams of (96% productive rate) light yellow oily products.
1H NMR(300MHz，CDCl 3)：δ8.20(d，J＝1.0Hz，1H)，7.83-7.74(m，2H)，7.46-7.40(m，1H)，7.36(s，2H)，7.25-7.19(m，1H)，7.01(s，1H)，2.43(s，6H).
Embodiment 21
N-(3, the 5-3,5-dimethylphenyl)-2 methyl indole
Figure A20061008248101251
Use general method A, make 2 methyl indole (165 milligrams, 1.26 mmoles) and 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ether 40: 1; 15 milliliters of flow points).Flow point 4-9 provides 232 milligrams of oily products that (95% productive rate) is colourless.
1H NMR(300MHz，CDCl 3)：δ7.62-7.53(m，1H)，7.15-7.05(m，4H)，6.98(s，2H)，6.39(s，1H)， 2.41(s，6H)，2.31(d，J＝1.0Hz，3H).
Embodiment 22
N-(2-methoxyphenyl) indoles
Figure A20061008248101252
Use general method A, make indoles (146 milligrams, 1.25 mmoles) and 2-iodoanisole (135 microlitres, 1.04 mmoles) combination.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ether 15: 1; 15 milliliters of flow points).Flow point 6-10 provides 232 milligrams of oily products that (100% productive rate) is colourless. 1Reports such as H NMR spectrum and Maiorana consistent.Maiorana，S.；Baldoli，C.；Del Buttero，P.；DiCiolo，M.；Papagni，A.Synthesis 1998，735.
Embodiment 23
1-(3, the 5-3,5-dimethylphenyl) pyrroles
Use general method B, pyrroles's (83 microlitres, 1.2 mmoles) is combined with 5-iodo-m-xylene, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 9: 1) obtain 0.170 gram (99% productive rate) colourless oily product.
1H NMR(400MHz，CDCl 3)：δ7.07(t，J＝7.0Hz，2H)，7.02(s，2H)，6.89(s，1H)，6.33(t，J＝7.0Hz，2H)，2.37(s，6H).
Embodiment 24
1-(3, the 5-3,5-dimethylphenyl)-1-pyrazoles
Figure A20061008248101262
Use general method B, use K 2CO 3(2.1 mmole) makes pyrazoles (0.082 gram, 1.2 mmoles) combine with 5-iodo-m-xylene as alkali, obtains thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 9: 1) obtain 0.153 gram (89% productive rate) colourless oily product.
1H NMR(400MHz，CDCl 3)：δ7.90(d，J＝2.2Hz，1H)，7.71(d，J＝1.5Hz，1H)，7.32(s，2H)，6.93(s，1H)，6.44(t，J＝2.2Hz，1H)，2.38(s，6H).
Embodiment 25
1-(3, the 5-3,5-dimethylphenyl)-1-(7-azaindole)
Use general method B, 7-azaindole (0.142 gram, 1.2 mmoles) is combined with 5-iodo-m-xylene, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 5: 1) obtain 0.220 gram (99% productive rate) white solid product.
1H NMR (400MHz, CDCl 3): δ 8.38 (dd, J=1.5Hz and J=4.7Hz, 1H), 7.97 (dd, J=1.5Hz and J=7.8Hz, 1H), 7.48 (d, J=3.6Hz, 1H), 7.33 (s, 2H), 7.12 (dd, J=4.7Hz and J=7.8Hz, 1H) 6.99 (s, 1H), 6.60 (d, J=3.6Hz, 1H), 2.41 (s, 6H).
Embodiment 26
1-(3, the 5-3,5-dimethylphenyl) carbazole
Use general method B, pyrroles's (83 microlitres, 1.2 mmoles) is combined with 5-iodo-m-xylene, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 50: 1) obtain 0.268 gram (99% productive rate) white solid product.
1H NMR(400MHz，CDCl 3)：δ8.15(d，J＝7.8Hz，2H)，7.41(m，4H)，7.28(m，2H)，7.18(s，2H)，7.11(s，1H)，2.43(s，6H).
Embodiment 27
1-(3, the 5-3,5-dimethylphenyl)-1-purine
Use general method B, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), Cs 2CO 3(2.1 mmole), anti--1, (24 microlitres, 0.20 mmole 20mol%) and dimethyl formamide (1.0 milliliters), make purine (0.144 gram, 1.2 mmoles) react with 5-iodo-m-xylene to the 2-cyclohexane diamine, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 1: 1) obtain 0.073 gram (33% productive rate) white solid product.
1H NMR(400MHz，CDCl 3)：δ9.24(s，1H)，9.06(s，1H)，8.34(s，1H)，7.31(s，2H)，7.13(s，1H)，2.44(s，6H).
Embodiment 28
1-(3, the 5-3,5-dimethylphenyl)-1-imidazoles
Figure A20061008248101281
Use general method B, and the use cuprous iodide (9.5 milligrams,, 0.050 mmole, 5.0mol%), Cs 2CO 3(2.1 mmole), anti--1, (24 microlitres, 0.20 mmole 20mol%) and dioxane (1.0 milliliters), make imidazoles (0.102 gram, 1.2 mmoles) react with 5-iodo-m-xylene to the 2-cyclohexane diamine, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 1: 4) obtain 0.142 gram (82% productive rate) clarification viscosity oily product.
1H NMR(400MHz，CDCl 3)：δ7.84(s，1H)，7.25(d，J＝1Hz，1H)，7.19(d，J＝1Hz，1H)，7.00(s，3H)，2.37(s，6H).
Embodiment 29
1-(3, the 5-3,5-dimethylphenyl)-1-benzoglyoxaline
Figure A20061008248101282
Use general method B, and the use cuprous iodide (0.019 gram, 0.10 mmole, 10mol%), Cs 2CO 3(2.1 mmole), 1, (0.036 gram, 0.20 mmole 20mol%) and dimethyl formamide (0.5 milliliter), make benzoglyoxaline (0.144 gram, 1.2 mmoles) react with 5-iodo-m-xylene to the 10-phenanthroline, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 1: 1) obtain 0.2 05 gram (92% productive rate) white solid products.
1H NMR(400MHz，CDCl 3)：δ8.10(s，1H)，7.87(m，1H)，7.55(m，1H)，7.33(m，2H)，7.13(s，2H)，7.10(s，1H)，2.43(s，6H).
Embodiment 30
1-(3, the 5-3,5-dimethylphenyl)-1-indazole
Figure A20061008248101291
Use general method B, but at room temperature make indazole (0.142 gram, 1.2 mmoles) and the reaction of 5-iodo-m-xylene.After filtering according to general method, the crude product reaction mixture is carried out gas chromatographic analysis, record 5 2% 5-iodo-m-xylene and be consumed.Record the ratio of title compound and 1-(3, the 5-3,5-dimethylphenyl)-2-indazole greater than 25 to 1 by the GC analysis.
Embodiment 31
N-(3, the 5-3,5-dimethylphenyl) benzamide
Figure A20061008248101292
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (4.0 milligrams, 0.0210 mmole, 1.0mol%), benzamide (300 milligrams, 2.48 mmoles), K 2CO 3(600 milligrams, 4.38 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (26 microlitres, 0.216 mmole, 11mol%), 5-bromo-m-xylene (280 microlitres, 2.06mmol) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 10-15 provides 419 milligrams of (90% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ7.92-7.85(m，3H)，7.59-7.75(m，3H)，7.31(s，2H)，6.82(s，1H)，2.34(s，6H). 13C NMR(100MHz，CDCl 3)：δ165.6，138.7，137.7，135.1，131.7，128.7，126，9，126.3，117.9，21.3.IR(neat，cm -1)：3300，1649，1614，1547.
Embodiment 32
N-(2-3,5-dimethylphenyl) benzamide
Figure A20061008248101301
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (6.0 milligrams, 0.0315 mmole, 1.0mol%), benzamide (460 milligrams, 3.80 mmoles), K 2CO 3(850 milligrams, 6.15 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (40 microlitres, 0.333 mmole, 11mol%), 2-bromo-phenylmethylether (0.38 milliliter, 3.05 mmoles) and dioxane (0.50 milliliter).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 5: 1; 20 milliliters of flow points).Flow point 10-15 provides 573 milligrams of oily products that (83% productive rate) is colourless.
1Reports such as H NMR spectrum and Narasaka consistent.
Tsutsi，H.；Ichikawa，T.；Narasaka，K.Bull.Chem.Soc.Jpn.1999，72，1869.
Embodiment 33
N-(4-methoxyphenyl)-2-azetidinone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (6.0 milligrams, 0.0315 mmole, 1.0mol%), 2-azetidinone (300 milligrams, 4.22 mmoles), K 2CO 3(850 milligrams, 6.15 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (40 microlitres, 0.333 mmole, 11mol%), 4-bromo-phenylmethylether (0.38 milliliter, 3.04 mmoles) and dioxane (0.50 milliliter).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 1; 20 milliliters of flow points).Flow point 10-22 provides 320 milligrams of (59% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ7.35-7.29(m，2H)，6.91-6.86(m，2H)，3.81(s，3H)，3.60(t，J＝4.4Hz，2H)，3.11(t，J＝4.4Hz，2H).
Embodiment 34
N-thiene-3-yl--benzamide
Figure A20061008248101311
Use general method C, make 3-bromo-thiophene and benzamide reaction 21 hours.Chromatography obtains 198.9 milligrams of (98%) solid state title compounds.
1H NMR(CDCl 3，300MHz)：δ8.34(br s，1H)，7.85(dd，2H，J＝1.2，8.1Hz)，7.72(dd，1H，J＝1.2，3.0Hz)，7.55-7.41(m，3H)，7.26(dd，1H，J＝3.3，4.8Hz)，7.14(dd，1H，J＝1.5，5.4Hz).
Embodiment 35
N-methyl-N-thiene-3-yl--methane amide
Figure A20061008248101312
Remove to use cuprous iodide (10 milligrams, 0.05 mmole, 5mol%) outside, use general method C, 3-bromo-thiophene and N-methylformamide were reacted 24 hours.Chromatography obtains 114 milligrams of (81%) oily title compounds.
1H NMR(CDCl 3，300MHz)：δ8.36(s，0.8H)，7.71(s，0.2H)，7.49(dd，0.2H，J＝1.5，5.4Hz)，7.08(dd，0.2H，J＝1.2，3.0Hz)，6.80(dd，0.2H，J＝3.3，5.4Hz)，6.64(dd，0.8H，J＝3.3，5.1Hz)，6.30(dd，0.8H，J＝1.8，5.4Hz)，5.98(dd，0.8H，J＝1.2，3.0Hz)，2.79(s，2.4H)，2.21(s，0.6H).
Embodiment 36
1-thiophene-2-base-pyrrolidin-2-one
Figure A20061008248101321
Use general method C, make 2-bromo-thiophene and 2-Pyrrolidone reaction 16 hours.Chromatography obtains 158 milligrams of (95%) solid state title compounds.
1H NMR(CDCl 3，300MHz)：δ6.94-6.86(m，2H)，6.53(br s，1H)，3.89(t，2H，J＝7.2Hz)，2.63(t，2H，J＝8.1Hz)，2.24(p，2H，J＝7.5Hz).
Embodiment 37
N-phenyl-N-thiene-3-yl--ethanamide
Use general method C, make 3-bromo-thiophene and Acetanilide reaction 15 hours.Chromatography obtains 178mg (82%) oily title compound.
1H NMR(CDCl 3，300MHz)：δ7.44(brs，3H)，7.28(s，2H)，7.18(s，2H)，6.94(d，1H，J＝4.8Hz)，1.99(br s，3H).
Embodiment 38
1-quinoline-3-base-pyrrolidin-2-one
Figure A20061008248101331
Use general method C, make 3-bromoquinoline and 2-Pyrrolidone reaction 15 hours.Chromatography obtains 210 milligrams of (99%) solid state title compounds.
1H NMR(CDCl 3，300MHz)：δ9.24(d，1H，J＝2.7Hz)，8.45(d，1H，J＝2.4 Hz)，8.08(d，1H，J＝8.4Hz)，7.82(d，1H，J＝8.1Hz)，7.66(t，1H，J＝7.7Hz)，7.55(t，1H，J＝7.5Hz)，4.04(t，2H，J＝7.2Hz)，2.69(t，2H，J＝8.1Hz)，2.28(p，2H，J＝7.8Hz).
Embodiment 39
Hexahydrobenzoic acid pyrimidine-5-base-acid amides
In the Schlenk pipe of drying that contains stirring rod that can seal again, pack into cuprous iodide (20 milligrams, 0.1 mmole, 10mol%), cyclohexane carboxamide (153 milligrams, 1.2 mmoles), 5-bromo pyrimi piperidine (160 milligrams, 1 mmole), and K 3PO 4(425 milligrams, 2 mmoles) find time and the filling argon gas.Injection N, N '-dimethyl-ethylenediamine (8.9 milligrams, 0.1 mmole) and dioxane (1 milliliter), and under argon gas stream, substitute barrier film with the tetrafluoroethylene nut.Seal this pipe, and this mixture stirred and heating 16 hours in 110 ℃ oil bath.Then material in the pipe is distributed between water and methylene dichloride.Separate water layer, and with twice of other dichloromethane extraction.In conjunction with organic layer, use dried over sodium sulfate, filter concentrating under reduced pressure.Silica gel chromatography purifying resistates is then used the dichloromethane/hexane recrystallization, obtains 154 milligrams of (75%) solid state title compounds.
1H NMR(CDCl 3，300MHz)：δ9.02(s，2H)，8.97(s，1H)，7.40(br s，1H)，2.32(tt，1H，J＝3.6，11.4Hz)，2.10-1.20(m，10H).
Embodiment 40
N-(4-aminomethyl phenyl) benzamide
Figure A20061008248101341
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), benzamide (250 milligrams, 2.06 mmoles), K 2CO 3(600 milligrams, 4.34 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (26 microlitres, 0.217 mmole, 10.5mol%), 4-toluene(mono)chloride (1.0 milliliters, 8.44 mmoles).Stirred 46 hours at 140 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained black suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Concentrate flow point 5-15, be suspended in 10 milliliters of hexanes solid residue and filtration, obtain 413 milligrams of (95% productive rate) white crystals shape products. 1Reports such as H NMR spectrum and Erdik consistent.Erdik，E.；Daskapan，T.J.Chem.Soc.，Perkin Trans.1 1999，3139.
Embodiment 41
N-(4-tolyl)-2-Pyrrolidone
Figure A20061008248101342
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), K 2CO 3(600 milligrams, 4.34 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (26 microlitres, 0.217 mmole, 11mol%), 2-Pyrrolidone (155 microlitres, 2.04 mmoles) and 4-toluene(mono)chloride (1.0 milliliters, 8.44 mmoles).Stirred 42 hours at 140 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 7; 20 milliliters of flow points).Flow point 10-20 provides 223 milligrams of (62% productive rate) white crystals shape products.
1Reports such as HNMR spectrum and Boeyens consistent.Billing，D.G.；Boeyens，J.C.A.；Denner，L.；Du Plooy，K.E.；Long，G.C.；Michael，J.P.Acta Cryst.(B)1991，B47，284.
Embodiment 42
N-(3, the 5-3,5-dimethylphenyl) phthalic imidine
The cuprous iodide (200 milligrams, 1.05 mmoles) of in the Schlenk pipe of drying that can seal again, packing into, phthalic imidine (185 milligrams, 1.25 mmoles), K 2CO 3(290 milligrams, 2.10 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (130 microlitres, 1.06 mmoles), dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 8-11 provides 34 milligrams of (13% productive rate) tawny solid state products. 1Reports such as H NMR spectrum and Hashimoto consistent.Shibata，Y.；Sasaki，K.；Hashimoto，Y.；Iwasaki，S.Chem.Pharm.Bull.1996，44，156.
Embodiment 43
N-(3, the 5-3,5-dimethylphenyl)-4-cyano-aniline
Figure A20061008248101352
In the Schlenk pipe of drying that can seal again, pack into (10 milligrams of cuprous iodides, 0.0525 mmole, 5.0mol%), 1,10-iodo-phenanthroline (20 milligrams, 0.111 mmole), (146 milligrams of 4-cyano-anilines, 1.24 milligram) sodium tert-butoxide (145 milligrams, 1.51 mmoles) is found time and the filling argon gas.Under argon atmospher, add dodecane (235 microlitre), 5-iodo-m-xylene (150 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 5: 1; 10 milliliters of flow points).Flow point 7-16 provides 159 milligrams of (69% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ7.51-7.47(m，2H)，6.91-6.95(m，2H)，6.83-6.80(m，2H)，6.80-6.78(m，1H)，6.02(brs，1H)，2.33(q，J＝0.5Hz，6H).
Embodiment 44
N-(3, the 5-3,5-dimethylphenyl)-methylphenylamine
Figure A20061008248101361
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (10 milligrams, 0.0525 mmole, 5.0mol%), 1,10-phenanthroline (20 milligrams, 0.111 mmole), sodium tert-butoxide (145 milligrams, 1.51 mmoles) is found time and the filling argon gas.Under argon atmospher, add dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), methylphenylamine (135 microlitres, 1.25 mmoles) and dioxane (1.0 milliliters).Stirred 24 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ether 50: 1; 10 milliliters of flow points).Flow point 7-11 provides 110 milligrams of oily products that (50% productive rate) is colourless.
1H NMR(400MHz，CDCl 3)：δ7.33-7.27(m，2H)，7.05-6.94(m，3H)，6.72(s，2H)，6.68(s，1H)，3.33(s，3H)，2.31(s，6H).
Embodiment 45
N-(3, the 5-3,5-dimethylphenyl)-1,2-is anti--cyclohexane diamine
The cuprous iodide (40 milligrams, 0.210 mmole) of in the Schlenk pipe of drying that can seal again, packing into, K 2CO 3(850 milligrams, 6.15 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (240 microlitres, 2.00 mmoles) and 5-iodine m-xylene (900 microlitres, 6.24 mmoles).Stirred 23 hours at 100 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained bluish voilet suspension cool to room temperature and by 2 * 1 centimetres of Celite pads, with 50 milliliters of methylene dichloride wash-outs.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; The saturated methylene chloride-methanol of aqueous ammonia 40: 1; 15 milliliters of flow points).Flow point 9-13 provides 178 milligrams of (41% productive rate) light tan solid state products.
1H NMR(400MHz，CDCl 3)：δ6.39(s，1H)，6.34(s，2H)，3.36(br s，1H)，3.03-2.92(m，1H)，2.56-2.46(m，1H)，2.25(s，6H)，2.20-2.10(m，1H)，2.08-1.95(m，1H)，1.83-1.70(m，2H)，1.55-1.20(m，5H)，1.10-1.00(m，1H).
Embodiment 46
N, N-two-(3, the 5-3,5-dimethylphenyl)-1,2-is anti--cyclohexane diamine
Figure A20061008248101372
The cuprous iodide (40 milligrams, 0.210 mmole) of in the Schlenk pipe of drying that can seal again, packing into, K 3PO 4(1.30 grams, 6.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (240 microlitres, 2.00 mmoles), 5-iodo-m-xylene (900 microlitres, 6.24 mmoles) and 2-methoxy ethyl ether (1.0 milliliters).Stirred 24 hours at 140 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 2 * 1 centimetres of Celite pads, with 50 milliliters of methylene dichloride wash-outs.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; The saturated chloroform-methanol of chloroform-aqueous ammonia 40: 40: 1; 15 milliliters of flow points).Flow point 7-14 provides 465 milligrams of (72% productive rate) tawny solid state products.
1H NMR(400MHz，CDCl 3)：δ6.67(s，1H)，6.57(s，2H)，3.65-3.55(m，1H)，2.68-2.58(m，1H)，2.28(s，12H)，2.08-1.92(m，2H)，1.83-1.64(m，2H)，1.58-1.10(m，6H).
Embodiment 47
N-(4-dimethylaminophenyl)-1,2-is anti--cyclohexane diamine
Figure A20061008248101381
The cuprous iodide (190 milligrams, 0.998 mmole) of in the Schlenk pipe of drying that can seal again, packing into, K 3PO 4(2.10 grams, 9.89 mmoles), 4-bromo-N, N '-xylidine (1.00 grams, 5.00 mmoles) finds time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (0.60L, 5.00 mmoles) and dioxane (3.0 milliliters).Stirred 70 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 2 * 1 centimetres of Celite pads, with 50 milliliters of methylene dichloride wash-outs.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; The saturated methylene chloride-methanol of aqueous ammonia 40: 1; 20 milliliters of flow points).Flow point 12-16 provides 692 milligrams of (59% productive rate) brown solid shape products.
1H NMR(400MHz，CDCl 3)：δ6.75-6.63(m，4H)，3.00(br s，1H)，2.87-2.77(m，7H)，2.53-2.45(m，1H)，2.17-2.04(m，1H)，2.02-1.94(m，1H)，1.78-1.16(m，7H)，1.04-0.92(m，1H). 13C NMR(100MHz，CDCl 3)δ144.7，140.9，116.2，116.1，62.0，56.5，42.6，35.7，33.0，25.8，25.5.
Embodiment 48
Use 1, the 10-phenanthroline is as the ligand preparation 3 of copper, 5-3,5-dimethylphenyl dimethyl malonate
Figure A20061008248101391
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (10 milligrams, 0.0525 mmole, 5.0mol%), 1,10-phenanthroline (20 milligrams, 0.111 mmole), Cs 2CO 3(460 milligrams, 1.41 mmoles) find time and the filling argon gas.Under argon atmospher, add dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), dimethyl malonate (145 microlitres, 1.27 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained grey suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 6: 1; 10 milliliters of flow points).Flow point 9-15 provides 216 milligrams of oily products that (88% productive rate) is colourless.
1H NMR(400MHz，CDCl 3)：δ7.03(s，2H)，7.00(s，1H)，4.61(s，1H)，3.77(s，6H)，2.35(s，6H). 13C NMR(100MHz，CDCl 3)δ169.2，138.7，132.7，130.5，127.3，57.8，53.2，21.7.
Embodiment 49
Use instead 1, the 2-cyclohexane diamine is as the ligand preparation 3 of copper, 5-3,5-dimethylphenyl dimethyl malonate
Figure A20061008248101392
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add dodecane (235 microlitre), anti--1,2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmole), dimethyl malonate (145 microlitres, 1.27 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained light yellow suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 5: 1; 20 milliliters of flow points).Flow point 10-16 provides 135 milligrams of oily products that (55% productive rate) is colourless.
Embodiment 50
(S)-O-(3, the 5-3,5-dimethylphenyl) amygdalic acid
Figure A20061008248101401
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 10mol%), (S)-amygdalic acid (190 milligrams, 1.25 mmoles), K 2CO 3(430 milligrams, 3.11 mmoles) find time and the filling argon gas.Under argon atmospher, add dodecane (235 microlitre), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), and N,N-dimethylacetamide (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.The gained light yellow suspension poured in 20 milliliter of 10% aqueous hydrochloric acid and with 3 * 20 milliliters dichloromethane extraction.With the organic phase drying (sodium sulfate) that merges, concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-ethyl acetate-acetate 40: 20: 1,15 milliliters of flow points).Flow point 7-13 provides 91 milligrams of (34% productive rate) white solid products.
1H NMR(400MHz，CDCl 3)：δ10.65(br s，1H)，7.64-7.57(m，2H)，7.47-7.36(m，3H)，6.67(s，1H)，6.61(s，2H)，5.65(s，1H)，2.28(s，6H).
Embodiment 51
N-(4-aminomethyl phenyl)-1,2-is anti--cyclohexane diamine
The cuprous iodide (190 milligrams, 0.998 mmole) of in the Schlenk pipe of drying that can seal again, packing into, K 3PO 4(2.10 grams, 9.89 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1,2-cyclohexane diamine (0.60 milliliter, 5.00 mmoles), 4-toluene bromide (0.70 milliliter, 5.69 mmoles) and dioxane (3.0 milliliters).Stirred 70 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 2 * 1 centimetres of Celite pads, with 50 milliliters of methylene dichloride wash-outs.Concentrate black filtrate, dodge (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; The saturated methylene chloride-methanol of aqueous ammonia 50: 1; 15 milliliters of flow points).Flow point 9-11 provides 650 milligrams of (64% productive rate) brown solid shape products.
1H NMR(400MHz，CDCl 3)：δ7.00-6.95(m，2H)，6.62-6.57(m，2H)，3.30(br s，1H)，2.96-2.86(br m，1H)，2.49(1d，J＝10.4，3.6，1H)，2.23(s，3H)，2.17-2.08(m，1H)，2.02-1.94(m，1H)，1.79-1.66(m，2H)，1.44(br s，2H)，1.38-1.17(m，3H)，1.07-0.95(m，1H). 13C NMR(100MHz，CDCl 3)δ145.9，129.7，126.6，113.9，60.5，56.1，35.2，32.4，25.3，25.0，20.3.
Embodiment 52
At room temperature use N-(4-aminomethyl phenyl)-anti--1, the 2-cyclohexane diamine prepares N-(3, the 5-3,5-dimethylphenyl) benzamide
Figure A20061008248101411
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (10 milligrams, 0.0525 mmole, 5.0mol%), anti--N-(4-aminomethyl phenyl)-1, the 2-cyclohexane diamine (22 milligrams, 0.108 mmole, 10mol%), benzamide (150 milligrams, 1.24 mmoles), Cs 2CO 3(650 milligrams, 1.99 mmoles) find time and the filling argon gas.Under argon atmospher, add dioxane (1.0 milliliters) and 5-iodine m-xylene (150 microlitres, 1.04 mmoles).With the Schlenk seal of tube and with reaction mixture magnetic stirring at room temperature 46 hours.Gained suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 8-15 provides 214 milligrams of (91% productive rate) white crystals shape products.
Embodiment 53
Use down N-(4-aminomethyl phenyl)-anti--1 at 50 ℃, the 2-cyclohexane diamine prepares N-(3, the 5-3,5-dimethylphenyl) benzamide
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), N-(4-aminomethyl phenyl)-anti--1, the 2-cyclohexane diamine (22 milligrams, 0.108 mmole, 1.0mol%), benzamide (150 milligrams, 1.24 mmoles), Cs 2CO 3(650 milligrams, 1.99 mmoles) find time and the filling argon gas.Under argon atmospher, add dioxane (1.0 milliliters) and 5-iodine m-xylene (150 microlitres, 1.04 mmoles).Stirred 23 hours at 50 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Gained light brown suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 9-14 provides 228 milligrams of (97% productive rate) pale pink look solid state products.
Embodiment 54
Use 1,3-two (2,4, the 6-trimethylphenyl)-imidazolium salts hydrochlorate prepares N-(3, the 5-3,5-dimethylphenyl) benzamide
In 10 milliliters of pyriform flasks, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.0mol%), 1,3-two (2,4, the 6-trimethylphenyl)-imidazolium salts hydrochlorate (36 milligrams, 5.1mol%), find time and the filling argon gas by 0.106 mmole.This flask is moved into glove box, and under nitrogen atmosphere, add NaOtBu (11 milligrams, 0.114 mmole, 5.5mol%).This flask is covered with barrier film and remove from glove box.Add dioxane (2.0 milliliters), gained light brown suspension was at room temperature stirred 15 minutes.Simultaneously, the benzamide of in the Schlenk pipe of drying that can seal again, packing into (300 milligrams, 2.48 mmoles), K 3PO 4(900 milligrams, 4.24 mmoles) find time and the filling argon gas.The effective rubber septum of this Schlenk is covered, and under argon atmospher, add 5-iodine m-xylene (300 microlitres, 2.08 mmoles).The catalyst suspension of above preparation is moved in the reaction mixture in the Schlenk pipe by thick sleeve pipe.The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.With gained brown suspension cool to room temperature, add dodecane (470 microlitres, GC standard), this mixture is filtered by Celite pad, use eluent ethyl acetate.GC analyzes the product that filtrate demonstration obtains 27% productive rate.
Embodiment 55
Use 1,3-two (2, the 6-diisopropyl phenyl)-tetrahydroglyoxaline  hydrochloride prepares N-(3, the 5-3,5-dimethylphenyl) benzamide
In 10 milliliters of pyriform flasks, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.0mol%), 1,3-two (2, the 6-diisopropyl phenyl) tetrahydroglyoxaline  hydrochloride (45 milligrams, 5.0mol%), find time and the filling argon gas by 0.105 mmole.This flask is moved into glove box, and under nitrogen atmosphere, add NaOtBu (11 milligrams, 0.114 mmole, 5.5mol%).This flask is covered with barrier film and remove from glove box.Add dioxane (2.0 milliliters), gained light brown suspension was at room temperature stirred 15 minutes.Simultaneously, the benzamide of in the Schlenk pipe of drying that can seal again, packing into (300 milligrams, 2.48 mmoles), K 3PO 4(900 milligrams, 4.24 mmoles) find time and the filling argon gas.The effective rubber septum of this Schlenk is covered, and under argon atmospher, add 5-iodine m-xylene (300 microlitres, 2.08 mmoles).The catalyst suspension of above preparation is moved in the reaction mixture in the Schlenk pipe by thick sleeve pipe.The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.With gained light brown suspension cool to room temperature, add dodecane (470 microlitres, GC standard), this mixture is filtered by Celite pad, use eluent ethyl acetate.GC analyzes the product that filtrate demonstration obtains 38% productive rate.
Embodiment 56
Use down 4-toluene(mono)chlorides and N at 110 ℃, N '-dimethyl-anti--1, and the 2-cyclohexane diamine prepares N-(4-aminomethyl phenyl) benzamide
Figure A20061008248101431
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), benzamide (250 milligrams, 2.06 mmoles), K 2CO 3(600 milligrams, 4.34 mmoles) find time and the filling argon gas.Add N under argon atmospher, N '-dimethyl-anti--1, and the 2-cyclohexane diamine (35 microlitres, 0.222 mmole, 11mol%), 4-toluene(mono)chloride (1.0 milliliters, 8.44 mmoles).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.With gained dark blue-green suspension cool to room temperature and filter by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrate light brown filtrate, dodge (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Concentrate flow point 4-10, be suspended in 10 milliliters of hexanes solid residue and filtration, obtain 392 milligrams of (90% productive rate) white fine needle shape products.
Embodiment 57
N-(2-methoxyphenyl) ethanamide
Figure A20061008248101441
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), ethanamide (180 milligrams, 3.05 mmoles), K 3PO 4((450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 2-iodoanisole (135 microlitres, 1.04 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 90 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained light green suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 20 milliliters of flow points).Flow point 10-16 provides 162 milligrams of (94% productive rate) white crystals shape products. 1H NMR spectrum is consistent with report.Hibbert，F.；Mills，J.F.；Nyburg，S.C.；Parkins，A.W.J Chem.Soc.，Perkin Trans.11998，629.
Embodiment 58
N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
Figure A20061008248101442
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).Stirred 24 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with gained light yellow suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 2; 20 milliliters of flow points).Flow point 12-23 provides 193 milligrams of (98% productive rate) white crystals shape products.
1H NMR(400MHz，CDCl 3)：δ7.23(s，2H)，6.82(s，1H)，3.85(t，J＝7.1Hz，2H)，2.61(t，J＝8.1Hz，2H)，2.34(s，6H)，2.16(tt，J＝8.1，7.1Hz，2H). 13C NMR(100MHz，CDCl 3)：δ174.1，139.2，138.4，126.3，118.0，49.1，32.8，21.5，18.1.IR(neat，cm -1)：1692，1596，1480，1393，1333，1247，852.Anal.Calcd for C 12H 15NO：C，76.16；H，7.99.Found：C，76.06；8.06.
Embodiment 59
Use cupric chloride (II) preparation N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into CuCI2 (1.5 milligrams, 0.0112 mmole, 1.1mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.Filter with the light brown suspension cool to room temperature of gained and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 9-18 provides 194 milligrams of (99% productive rate) white crystals shape products.
Embodiment 60
Use copper powder production N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into copper powder (1.5 milligrams, 0.0236 mmole, 1.1mol%), K 3PO 4(900 milligrams, 4.24 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (2 6 microlitres, 0.217 mmole, 10mol%), 5-iodine m-xylene (300 microlitres, 2.08 mmoles), 2-Pyrrolidone (190 microlitres, 2.50 mmoles) and dioxane (2.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.With gained light brown suspension cool to room temperature, add dodecane (235 microlitres, GC standard), this mixture is filtered by Celite pad, use eluent ethyl acetate.GC analyzes the product that filtrate demonstration obtains 99% productive rate.
Embodiment 61
Under nitrogen atmosphere, prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and filling nitrogen.Under nitrogen atmosphere, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.With gained light brown suspension cool to room temperature, add dodecane (235 microlitres, GC standard), this mixture is filtered by Celite pad, use eluent ethyl acetate.GC analyzes the product that filtrate demonstration obtains 99% productive rate.
Embodiment 62
In air, prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone pyrrolidone
Under air atmosphere, and the cuprous iodide of in the Schlenk pipe of drying that can seal again, packing into (2.0 milligrams, 0.0105 mmole, 1.0mol%) and K 3PO 4(450 milligrams, 2.12 mmoles).Under air atmosphere, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).Stirred 23 hours at 110 ℃ of magnetic with the Schlenk seal of tube and with reaction mixture.With gained light brown suspension cool to room temperature, add dodecane (235 microlitres, GC standard), this mixture is filtered by Celite pad, use eluent ethyl acetate.GC analyzes the product that filtrate demonstration obtains 95% productive rate.
Embodiment 63
The general method of N-H heterocyclic arylization
The cuprous iodide of packing in the flame-dried Schlenk pipe that can seal again, heterogeneous ring compound (1.2 mmole) and alkali (2.1 mmole) are found time twice and the filling argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) then successively, t12whalide, anti--1,2-cyclohexane diamine and dioxane.Stirred 20 hours in 110 ℃ oil bath with the Schlenk seal of tube and with reaction mixture.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Concentrated filtrate by column chromatography purification gained resistates, obtains purified product.
Embodiment 64
2-(3, the 5-3,5-dimethylphenyl)-1-2, the 3-phthalazone
Figure A20061008248101471
Use the general method of embodiment 63, and the use cuprous iodide (5.7 milligrams, 0.030 mmole, 3.0mol%), Cs 2CO 3(2.1 mmole), anti--1,2-cyclohexane diamine (24 microlitres, 0.20 mmole, 20mol%) and dioxane (0.5 milliliter), make 2 ketone (0.175 gram, 1.2 mmole), obtain thick product with 5-iodo-m-xylene (144 microlitres, 1.00 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 10: 1) obtain 0.225 gram (90% productive rate) white solid product.
1H NMR(400MHz，CDCl 3)：δ8.52(d，J＝7.3Hz，1H)，8.28(s，1H)，7.79-7.87(m，2H)，7.74-7.47(m，1H)，7.25(bs，2H)，7.04(s，1H)，2.40(s，6H).
Embodiment 65
1-(4-aminomethyl phenyl)-indoles
Figure A20061008248101472
Use the general method of embodiment 63, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--1, (24 microlitres, 0.20 mmole 20mol%) and dioxane (1.0 milliliters), make indoles (0.117 gram, 1.00 mmoles) react with 4-toluene bromide (185 microlitres, 1.50 mmoles) to the 2-cyclohexane diamine, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 50: 1) obtain 0.197 gram (95% productive rate) white solid product.By 1H NMR compares with known collection of illustrative plates, proves that this product is pure.
Embodiment 66
The selectivity preparation of 1-(4-aminomethyl phenyl)-indoles
Use the general method of embodiment 63, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--1, (24 microlitres, 0.20 mmole 20mol%), make indoles (0.117 gram, 1.00 mmoles) and 4-toluene(mono)chloride (1 milliliter, 8.45 mmoles) reaction to the 2-cyclohexane diamine, obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 50: 1) obtain 0.066 gram (32%GC productive rate) white solid product.By 1H NMR compares with known collection of illustrative plates, proves that this product is pure.
Embodiment 67
1-(4-aminomethyl phenyl)-2-phenylindone
Use the general method of embodiment 63, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--1,2-cyclohexane diamine (24 microlitres, 0.20 mmole 20mol%) and dioxane (0.5 milliliter), makes 2-phenylindone (0.232 gram, 1.20 mmole), obtain thick product with 5-iodine m-xylene (144 microlitres, 1.00 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 10: 1) obtain 0.220 gram (74% productive rate) white solid product.
1H NMR(400MHz，CDCl 3)：δ7.92(m，1H)，7.55(m，3H)，7.47(m，3H)，7.41(m，2H)，7.20(bs，1H)，7.13 (bs，2H)，7.05(d，1H，J＝0.6Hz)，2.52(s，6H). 13C NMR(100MHz，CDCl 3)：δ140.63，139.10，138.82，138.29，132.60，128.90，128.70，128.14，128.03，127.12，125.66，122.09，120.48，120.39，21.19.
Embodiment 68
1-(3, the 5-3,5-dimethylphenyl)-5-methoxyl group indoles
Use the general method of embodiment 63, and the use cuprous iodide (2.0 milligrams, 0.010 mmole, 1.0mol%), K 3PO 4(2.1 mmole), anti--1,2-cyclohexane diamine (12 microlitres, 0.10 mmole 10mol%) and dioxane (1.0 milliliters), makes 5-dimethoxy indoles (0.177 gram, 1.20 mmole), obtain thick product with 5-iodine m-xylene (144 microlitres, 1.00 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 50: 1) obtain 0.250 gram (100% productive rate) white solid product.
1H NMR (400MHz, CDCl 3): δ 7.66 (d, 1H, J=8.9Hz), 7.43 (d, 1H, J=3.2Hz), 7.32 (d, 1H, J=3.3Hz), 7.27 (bs, 2H), 7.12 (bs, 1H), 7.07 (dd, 1H, J=2.4Hz and J=9.0Hz), 6.75 (d, 1H, J=2.2Hz), 4.02 (s, 3H), 2.54 (s, 6H). 13C NMR (100MHz, CDCl 3): δ 154.33,139.68,139.20,130.93,129.71,128.26,127.78,121.58,112.20,111.37,102.80,102.45,55.58,21.20.
Embodiment 69
Use cis-and anti--1,2-cyclohexane diamine mixture prepares N-(4-methoxyphenyl)-N-methylformamide
Figure A20061008248101491
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (10 milligrams, 0.0525 mmole, 5.0mol%), Cs 2CO 3(460 milligrams, 1.41 mmoles) find time and the filling argon gas.Under argon atmospher, add 1,2-cyclohexane diamine (mixture of genial trans isomer, 13 microlitres, 0.106 mmole, 10mol%), N-methylformamide (72 microlitres, 1.23 mmole), 4-iodoanisole (245 milligrams, 1.05 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 22 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with the light brown suspension cool to room temperature of gained and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 10 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 2; 15 milliliters of flow points).Flow point 16-29 provides 158 milligrams of oily products that (91% productive rate) is colourless. 1Reports such as HNMR spectrum and Hoffman consistent.Hoffman et al.J.Org.Chem.1992，57，4487.
Embodiment 70
N-tertbutyloxycarbonyl-N-(3, the 5-3,5-dimethylphenyl) aniline
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), N-tertbutyloxycarbonyl aniline (200 milligrams, 1.04 mmoles), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (190 microlitres, 1.32 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with gained light yellow suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 20: 1; 20 milliliters of flow points).Flow point 12-20 provides 299 milligrams of (97% productive rate) white crystals shape products.[121 pages of Fig. 2 of original text]
1H NMR (400MHz, CDCl 3): δ 7.36-7.30 (m, 2H), 7.27-7.16 (m, 3H), 6.87 (s, 2H), 6.85 (s, 1H), 2.30 (s, 6H), 1.48 (s, 9H). 13C NMR (100MHz, CDCl 3): δ 153.9,143.2,142.7,138.3,128.6,127.5,126.9,125.4,124.8,80.9,28.2,21.2. analysis of control C 19H 23NO 2: C, 76.74; H, 7.79. actual measurement: C, 76.61; 7.87.
Embodiment 71
At room temperature use N-(4-dimethylaminophenyl)-anti--1, the 2-cyclohexane diamine prepares N-(3, the 5-3,5-dimethylphenyl) benzamide
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (10 milligrams, 0.0525 mmole, 5.0mol%), N-(4-dimethylaminophenyl)-anti--1, the 2-cyclohexane diamine (25 milligrams, 0.107 mmole, 10mol%), benzamide (150 milligrams, 1.24 mmoles), Cs 2CO 3(650 milligrams, 1.99 mmoles) find time and the filling argon gas.Under argon atmospher, add dioxane (1.0 milliliters) and 5-iodine m-xylene (150 microlitres, 1.04 mmoles).With Schlenk test tube usefulness tetrafluoroethylene valve channel closure and with reaction mixture magnetic stirring at room temperature 23 hours.Gained light brown suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrate mulberry-brown filtrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points).Flow point 7-15 provides 208 milligrams of (89% productive rate) light yellow solid shape products.
Embodiment 72
Use quadrol to prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
Figure A20061008248101511
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add quadrol (15 microlitres, 0.224 mmole, 22mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with the light brown suspension cool to room temperature of gained and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 9-18 provides 191 milligrams of (97% productive rate) white crystals shape products.
Embodiment 73
Use thanomin to prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add thanomin (12 microlitres, 0.199 mmole, 19mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with gained light brown suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 10-18 provides 136 milligrams of (69% productive rate) white crystals shape products. 1H NMR spectrum is consistent with above report.
Embodiment 74
Under 110 ℃, in 60 minutes, prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (2.0 milligrams, 0.0105 mmole, 1.0mol%), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--1, the 2-cyclohexane diamine (13 microlitres, 0.108 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 60 minutes at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with the light blue suspension cool to room temperature of gained and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 10-20 provides 176 milligrams of (89% productive rate) white crystals shape products. 1H NMR spectrum is consistent with above report.
Embodiment 75
Use down 4-toluene(mono)chlorides and N at 130 ℃, N '-dimethyl-anti--1, and the 2-cyclohexane diamine prepares N-(4-aminomethyl phenyl)-2-Pyrrolidone
Figure A20061008248101521
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), K 2CO 3(600 milligrams, 4.34 mmoles) find time and the filling argon gas.Add N under argon atmospher, N '-dimethyl-anti--1, and the 2-cyclohexane diamine (35 microlitres, 0.222 mmole, 11mol%), 2-Pyrrolidone (155 microlitres, 2.04 mmoles) and 4-toluene(mono)chloride (1.0 milliliters, 8.44 mmoles).The Schlenk test tube was stirred 23 hours at 130 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 4; 15 milliliters of flow points).Flow point 7-15 provides 336 milligrams of (94% productive rate) white crystals shape products.
Embodiment 76
Use down 4-chloroanisoles and N at 130 ℃, N '-dimethyl-anti--1, and the 2-cyclohexane diamine prepares N-(4-p-methoxy-phenyl)-2-Pyrrolidone
Figure A20061008248101531
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), K 2CO 3(600 milligrams, 4.34 mmoles) find time and the filling argon gas.Add N under argon atmospher, N '-dimethyl-anti--1, and the 2-cyclohexane diamine (35 microlitres, 0.222 mmole, 11mol%), 2-Pyrrolidone (155 microlitres, 2.04 mmoles) and 4-chloroanisole (1.0 milliliters, 8.16 mmoles).The Schlenk test tube was stirred 23 hours at 130 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with gained brown suspension cool to room temperature and by 0.5 * 1cm silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Ethyl acetate; 20 milliliters of flow points).Flow point 7-15 provides 188 milligrams of (48% productive rate) white solid products. 1People such as H NMR spectrum and Easton report consistent.Easton，C.J.；Pitt，M.J.；Ward，C.M.Tetrahedron 1995，51，12781.
Embodiment 77
Use down 4-chloro benzoic ethers and N at 110 ℃, N '-dimethyl-anti--1, and the 2-cyclohexane diamine prepares N-(4-methoxycarbonyl phenyl)-2-Pyrrolidone
In the Schlenk pipe of drying that can seal again, pack into cuprous iodide (20 milligrams, 0.105 mmole, 5.1mol%), 4-chloro benzoic ether (1.40 gram, 8.21 mmoles), K 2CO 3(600 milligram of 4.34 mmole) finds time and the filling argon gas tout court.Add N under argon atmospher, N '-dimethyl-anti--1, and the 2-cyclohexane diamine (35 microlitres, 0.222 mmole, 11mol%), 2-Pyrrolidone (155 microlitres, 2.04 mmoles).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Filter with gained pale green brown suspension cool to room temperature and by 2 * 0.5 centimetres of silicagel pad, with 30 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 4; 15 milliliters of flow points).Flow point 10-19 provides 266 milligrams of (59% productive rate) white crystals shape products. 1Reports such as H NMR spectrum and Atigadda consistent.Atigadda，V.R.；Brouillette，W.J.；Duarte，F.；Ali，S.M.；Babu，Y.S.；Bantia，S.；Chand，P.；Chu，N.；Montgomery，J.A.；Walsh，D.A.；Sudbeck，E.A.；Finley，J.；Luo，M.；Air，G.M.；Laver，G.W.J.Med.Chem.1999，42，2332.
Embodiment 78
Copper catalytic aminoization (glycol system)
The general method of copper catalytic aminoization under argon atmospher (5mol% cuprous iodide catalyst)
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole) and anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.00 mmoles).This pipe is found time and use the argon gas backfill.At room temperature add Virahol (1.0 milliliters) successively, ethylene glycol (111 microlitres, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles) and phenyl-iodide (112 microlitres, 1.00 mmoles) by micro-syringe.This reaction is heated to 80 ℃, given a kind of light yellow suspension.Should react and heat preset time, and make it reduce to room temperature then.In reaction mixture, add ether (2 milliliters) and water (2 milliliters).Analyze organic layer by GC.By the further extractive reaction mixture of ether (4 * 10 milliliters).With organic phase water or the salt water washing that merges, with sodium sulfate or dried over mgso.Except that desolvating, the brown resistates that obtains is passed through purification by silica gel column chromatography by rotary evaporation,, obtain weak yellow liquid shape product with solvent mixture (hexane/ethyl acetate=20/1) wash-out.
Amidized general method under argon atmospher (1mol% cuprous iodide catalyst)
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (2.0 milligrams, 0.01 mmole) and anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.00 mmoles).This pipe found time and with argon gas backfill three times.At room temperature add Virahol (1.0 milliliters) successively, ethylene glycol (111 microlitres, 2.00 mmoles), amine (1.20 mmole) and aryl iodide (1.00 mmole) by micro-syringe.80 ℃ of times that heating is given, make it reduce to room temperature then this reaction mixture.In reaction mixture, add ether (2 milliliters) and water (2 milliliters).Analyze organic layer by GC.By the further extractive reaction mixture of ether (4 * 10 milliliters).With organic phase water or the salt water washing that merges, use dried over sodium sulfate.Except that desolvating, the resistates that obtains is passed through purification by silica gel column chromatography by rotary evaporation, use the hexane/ethyl acetate wash-out, obtain the shape product that needs.
The general method of copper catalytic aminoization under atmospheric condition
With (10 milligrams of cuprous iodides (I), 0.05 mmole) and (425 milligrams of anhydrous phosphoric acid potassium fine powders, 2.00 the test tube that tetrafluoroethylene barrier film spiral covers of packing into mmole), then at room temperature add Virahol (1.0 milliliters) by micro-syringe, ethylene glycol (111 microlitres, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmole) and phenyl-iodide (112 microlitres, 1.00 mmoles).Be heated to 80 ℃ with this test tube covering and with this reactant, obtain a kind of light yellow suspension.Should react and heat preset time, and make it reduce to room temperature then.In reaction mixture, add ether (2 milliliters) and water (2 milliliters).Analyze organic layer by GC.By the further extractive reaction mixture of ether (4 * 10 milliliters).With organic phase water or the salt water washing that merges, with sodium sulfate or dried over mgso.Except that desolvating, the brown resistates that obtains is passed through purification by silica gel column chromatography by rotary evaporation,, obtain weak yellow liquid shape product with solvent mixture (isohexane ethyl acetate=20/1) wash-out.
N-(phenyl) benzylamine (Fig. 1, clauses and subclauses 1 and 2)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), Virahol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.6) wash-out obtain N-(phenyl) benzylamine (166 milligrams, 91% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Apodaca, R.; Xiao, W.Org.Lett.2001,3,1745-1748.
4-(N-benzyl) aminoacetophenone (Fig. 1, clauses and subclauses 3 and 4)
Under argon atmospher, use cuprous iodide (I) (2.0 milligrams, 0.01 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-phenyl-iodide ethyl ketone (246 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.2) wash-out obtain yellow solid shape 4-(N-benzyl) aminoacetophenone (203 milligrams, 90% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Nose, A.; Kudo, T.Chem.Pharm.Bull.1986,34,4817-4820.
4-(N-benzyl) aminobenzonitrile (Fig. 1, clauses and subclauses 5)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-iodo benzonitrile (229 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.4) wash-out obtain faint yellow solid shape 4-(N-benzyl) aminobenzonitrile (164 milligrams, 79% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Wolfe, J.P.; Tomori, H.; Sadighi, J.P.; Yin, J.; Buchwald, S.L.J.Org.Chem.2000,65,1158-1174.
N-(4-chloro-phenyl-) benzylamine (Fig. 1, clauses and subclauses 6)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-chloro benzonitrile (239 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=10/1, Rf=0.4) wash-out obtain weak yellow liquid shape N-(4-chloro-phenyl-) benzylamine (182 milligrams, 84% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Burton, R.D.; Bartberger, M.D.; Zhang, Y.; Eyler, J.R.; Schanze, K.S.J.Am.Chem.Soc.1996,118,5655-5664.
N-benzyl-4-anisidine (Fig. 1, clauses and subclauses 7)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-iodo phenylmethylether (234 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography uses solvent mixture benzyl hexane/ethyl acetate=10/1, and Rf=0.4) wash-out obtains faint yellow solid shape N-benzyl-4-anisidine (192 milligrams, 90% isolated yield).Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
N-(4-tolyl) benzylamine (Fig. 1, clauses and subclauses 8)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-toluene iodide (218 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid N-(4-tolyl) benzylamine (169 milligrams, 86% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
The amino m-xylene of 5-(N-benzyl) (Fig. 1, clauses and subclauses 9 and 10)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 5-iodine m-xylene (144 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain the amino m-xylene of colourless liquid 5-(N-benzyl) (177 milligrams, 84% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Wolfe, J.P.; Buchwald, S.L.J.Org.Chem.2000,65,11441157.
N-(3-bromophenyl) benzylamine (Fig. 1, clauses and subclauses 11-13)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole or 2.0 milligrams, 0.01 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1,1.20 mmole), 3-bromo-iodobenzene (128 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.4) wash-out obtain colourless liquid N-(3-bromophenyl) benzylamine (217 milligrams, 83% isolated yield) to use solvent mixture.Spectroscopic data ( 1HNMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Beletskaya, I.P.; Bessmertnykh, A.G.; Guilard, R.Synlett 1999,1459-1461.
N-(3-cyano-phenyl) benzylamine (Fig. 1, clauses and subclauses 14)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 3-iodine benzonitrile (229 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.5) wash-out obtain faint yellow solid shape N-(3-cyano-phenyl) benzylamine (165 milligrams, 80% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
N-(3-trifluoromethyl) benzylamine (Fig. 1, clauses and subclauses 15 and 16)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 3-iodine benzonitrile (144 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.4) wash-out obtain colourless liquid N-(3-trifluoromethyl) benzylamine (229 milligrams, 91% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Desmurs, J.R.; Lecouve, J.P.; Kempf, H.; Betremieux, I.; Ratton, S.New J.Chem.1992,16,99-106.
N-(3-methoxyphenyl) benzylamine (Fig. 1, clauses and subclauses 17)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 3-iodo phenylmethylether (119 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=10/1, Rf=0.4) wash-out obtain white solid N-(3-methoxyphenyl) benzylamine (171 milligrams, 80% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Ali, M.H.; Buchwald, S.L.J.Org.Chem.2001,66,2560-2565.
N-(3-nitrophenyl) benzylamine (Fig. 1, clauses and subclauses 18)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (109 microlitres, 1.00 mmoles), 3-iodonitrobenzene (349 milligrams, 1.40 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.4) wash-out obtain orange solids shape N-(3-nitrophenyl) benzylamine (164 milligrams, 7 2% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%. referring to Leardini, R.; Nanni, D.; Tundo, A.; Zanardi, G.; Ruggieri, F.J.Org.Chem.1992,57,1842-1848.
N-(3-tolyl) benzylamine (Fig. 1, clauses and subclauses 19)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 3-toluene iodide (128 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid N-(3-tolyl) benzylamine (171 milligrams, 87% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Spagnolo, P.; Zanirato, P.TetrahedronLett.1987,28,961-964.
N-(2-tolyl) benzylamine (Fig. 1, clauses and subclauses 20)
Under argon gas or air atmosphere, use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-toluene iodide (127 microlitres, 1.00 Bo moles), ethylene glycol (111 microlitres, 2.00 mmoles), 1-butanols (1.0 milliliters) is implemented general method at 100 ℃.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid N-(2-tolyl) benzylamine (136 milligrams, 69% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Maccarone, E.; Mamo, A.; Torre, M.J.Org.Chem.1979,44,11431146.
N-(2-methoxyphenyl) benzylamine (Fig. 1, clauses and subclauses 21)
Under argon gas or air atmosphere, use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-iodoanisole (130 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 1-butanols (1.0 milliliters) is implemented general method at 100 ℃.Column chromatography, (hexane/ethyl acetate=10/1, Rf=0.4) wash-out obtain colourless liquid N-(2-methoxyphenyl) benzylamine (149 milligrams, 70% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
2-(N-benzyl) benzaminic acid (Fig. 1, clauses and subclauses 22-24)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4636 milligrams, 3.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-iodo-benzoic acid (248 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.After the time length that heating specifies, make reactant reach room temperature.Adding entry and dilute hydrochloric acid (10%) is 3 up to the pH value.Add ether (2 milliliters) and analyze organic layer by tlc.Further by ether (4 * 10 milliliters) extractive reaction mixture, with the organic phase that merges with the salt water washing and use dried over sodium sulfate.The rotary evaporation solvent, by column chromatography purification yellowish brown resistates, (ether/ethyl acetate=1/1, Rf=0.3) wash-out obtain faint yellow solid shape 2-(N-benzyl) benzaminic acid (161 milligrams, 71% isolated yield) to use solvent mixture.For the aryl bromide substrate: use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(636 milligrams, 3.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-bromo-benzoic acid (201 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 1-butanols (1.0 milliliters) and be heated to 100 ℃.Continue to use aforesaid method, obtain faint yellow solid shape 2-(N-benzyl) benzaminic acid (120 milligrams, 53% isolated yield).For the aryl chloride substrate: use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(636 milligrams, 3.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-chloro-benzoic acid (157 milligrams, 1.00 Bo moles), ethylene glycol (111 microlitres, 2.00 mmoles) and 1-butanols (1.0 milliliters) and be heated to 100 ℃.Continue to use aforesaid method, obtain faint yellow solid shape 2-(N-benzyl) benzaminic acid (109 milligrams, 48% isolated yield).Spectroscopic data ( 1HNMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Chang, M.R.; Takeuchi, Y.; Hashigaki, K.; Yamato, M.Heterocycles1992,33,147-152.Moore, J.A.; Sutherland, G.J.; Sowerby, R.; Kelly, E.G.; Palermo, S.; Webster, W.JOrg.Chem.1969,34,887-892.
2-(N-benzyl) amino-benzene methyl alcohol (Fig. 1, clauses and subclauses 25)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.5 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-iodine benzyloxy benzonitrile alcohol (234 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=4/1, Rf=0.3) wash-out obtain pale solid shape 2-(N-benzyl) amino-benzene methyl alcohol (203 milligrams, 95% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Coppola, G.A.J.Herterocyl.Chem.1986,23,223-224.
4-(N-benzyl) amino aniline (Fig. 1, clauses and subclauses 26)
Under argon atmospher, use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (218 microlitres, 2.0 mmoles), 4-Iodoaniline (219 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method at 90 ℃.Column chromatography, (hexane/ethyl acetate=2/1 is to 1/1, and Rf=0.2) wash-out obtains brown solid shape 4-(N-benzyl) amino aniline (101 milligrams, 51% isolated yield) to use gradient solvent.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Araki, T.; Tsukube, H.J.Polym.Sci., Polym.Lett.Ed.1979,17,501-505.
4-(N-benzyl) subcutin (Fig. 1, clauses and subclauses 27)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 4-iodo ethyl benzoate (167 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and ethanol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.4) wash-out obtain faint yellow solid shape 4-(N-benzyl) subcutin (113 milligrams, 50% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Albright, J.D.; DeVries, V.G.; Largis, E.E.; Miner, T.G.Reich, M.F.; Schaffer, S.; Shepherd, R.G.; Upeslacis, J.J.Med.Chem.1983,26,13781393; And Onaka, M.; Umezono, A.; Kawai, M.; Izumi, Y.J.Chem.Soc., Chem.Commun.1985,1202-1203.
N-(1-naphthyl) benzylamine (Fig. 1, clauses and subclauses 28)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 1-iodine naphthalene (146 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.4) wash-out obtain faint yellow solid shape N-(1-naphthyl) benzylamine (163 milligrams, 70% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Janin, Y.L.; Bisagni, E.Synthesis1993,57-59.
N-(phenyl) hexylamine (Fig. 2, clauses and subclauses 2-4)
Under argon gas or air atmosphere, and use cuprous iodide (I) (10 milligrams, 0.05 mmole or 2.0 milligrams, 0.01 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), hexylamine (159 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid shape N-(phenyl) hexylamine (152 milligrams, 86% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Bomann, M.D.; Guch, 1.C.; DiMare, M.J.Org Chem.1995,60,5995-5996.
N (2-methoxy ethyl) aniline (Fig. 2, clauses and subclauses 5-7)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole or 2.0 milligrams, 0.01 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), 2-methoxyethyl amine (104 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=10/1, Rf=0.2) wash-out obtain colourless liquid N-(2-methoxy ethyl) aniline (138 milligrams, 91% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Fancher, L.W.; Gless, R.D., Jr.; Wong, R.Y.Tetrahedron Lett.1988,29,5095-5098.
N-(phenyl)-α-Jia Jibianji amine (Fig. 2, clauses and subclauses 8)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), α-Jia Jibianji amine (155 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid shape N-(phenyl)-α-Jia Jibianji amine (144 milligrams, 73% isolated yield) to use solvent mixture.HPLC condition: (post: Daicel OD-H; Solvent: 10% in the hexane iPrOH; Flow velocity: 0.7mL/min; UV lamp:254nm; Retention time: 6.01,6.78 minutes).Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A.J.Am.Chem.Soc.1999,121,6421-6429.
(R)-N-(phenyl)-α-Jia Jibianji amine (Fig. 2, clauses and subclauses 9)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), (R)-α-Jia Jibianji amine (155 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and Virahol (1.0 milliliters) are implemented general method.Column chromatography, use solvent mixture (hexane/ethyl acetate=20/1, Rf=0.5) wash-out, obtain colourless liquid shape (R)-N-(phenyl)-α-Jia Jibianji amine (150 milligrams, 76% isolated yield, 99%ee).HPLC condition: (post: Daicel OD-H; Solvent: 10% in the hexane iPrOH; Flow velocity: 0.7mL/min; UV lamp:254nm; Retention time: 6.74min). spectroscopic data ( 1HNMR) consistent with reference, GC analyzes and shows purity＞95%.
N-methyl-N-phenylbenzyl amine (Fig. 2, clauses and subclauses 10)
Under argon atmospher, use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), N-methyl-benzyl amine (155 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 1-butanols (1.0 milliliters) is implemented general method at 90 ℃.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.5) wash-out obtain colourless liquid shape N-methyl-N-phenylbenzyl amine (146 milligrams, 74% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Brenner, E.; Schneider, R.; Fort, Y.Tetrahedron 1999,55,12829-12842.
N-(phenyl) Pyrrolidine (Fig. 2, clauses and subclauses 11-13)
Under argon gas or air atmosphere, use cuprous iodide (I) (10 milligrams, 0.05 mmole or 2.0 milligrams, 0.01 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), Pyrrolidine (100 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.4) wash-out obtain colourless liquid shape N-(phenyl) Pyrrolidine (133 milligrams, 90% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Ishikawa, T.; Uedo, E.; Tani, R.; Saito, S.J.Org.Chem.2001,66,186-191.
N-(phenyl) piperidines (Fig. 2, clauses and subclauses 14)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), piperidines (119 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.4) wash-out obtain colourless liquid shape N-(phenyl) piperidines (129 milligrams, 80% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Beller, M.; Breindl, C.; Riermeier, T.H.; Tillack, A.J.Org.Chem.2001,66,1403-1412; And Li, G.Y.Angew.Chem., Int.Ed.2001,40,1513-1516.
N-(phenyl) morpholine (Fig. 2, clauses and subclauses 15)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), morpholine (130 microlitres, 1.50 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.2) wash-out obtain colourless liquid shape N-(phenyl) morpholine (124 milligrams, 76% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Desmarets, C.; Schneider, R.; Fort, Y.TetrahedronLett.2000,41,28752879.
N-phenyl-N '-(methyl) piperazine (Fig. 2, clauses and subclauses 16)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), N-(methyl) piperazine (166 microlitres, 1.50 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.Column chromatography, (hexane/ethyl acetate=20/1, Rf=0.1) wash-out obtain colourless liquid shape N-phenyl-N '-(methyl) piperazine (125 milligrams, 71% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
N-phenyl-L-proline(Pro) (Fig. 2, clauses and subclauses 17)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), L-proline(Pro) (138 milligrams, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method.After the time length that heating specifies, make reactant reach room temperature.Adding entry and dilute hydrochloric acid (10%) is 3 up to the pH value.Add ether (2 milliliters) and analyze organic layer by tlc.Further by ether (4 * 10 milliliters) extractive reaction mixture, with the organic phase that merges with the salt water washing and use dried over sodium sulfate.The rotary evaporation solvent, by column chromatography purification yellowish brown resistates, (ether/ethyl acetate=1/1, Rf=0.2) wash-out obtain faint yellow solid shape N-phenyl-L-proline(Pro) (134 milligrams, 70% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F.J.Am.Chem.Soc.1998,120,12459-12467.
N-(phenyl) aniline (Fig. 2, clauses and subclauses 18)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), aniline (109 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) are implemented general method at 90 ℃.Column chromatography, (hexane/ethyl acetate=5/1, Rf=0.4) wash-out obtain faint yellow solid shape N-(phenyl) aniline (69 milligrams, 41% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.
N-(phenyl)-2-Pyrrolidone (Fig. 2, clauses and subclauses 21)
Under argon atmospher, use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(425 milligrams, 2.00 mmoles), 2-Pyrrolidone (91 microlitres, 1.20 mmoles), phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles), 2-propyl alcohol (1.0 milliliters) is implemented general method at 90 ℃.Column chromatography, (hexane/ethyl acetate=1/1, Rf=0.4) wash-out obtain white solid N-(phenyl)-2-Pyrrolidone (80 milligrams, 50% isolated yield) to use solvent mixture.Spectroscopic data ( 1H NMR) consistent with reference, GC analyzes and shows purity＞95%.Referring to Yin, J.; Buchwald, S.L.Org.Lett.2000,2,1101-1104; And Kang, S.-K.; Lee, S.-H.; Lee, D.Synlett2000,1022-1024.
N-(4-methoxyphenyl) hexahydroaniline (Fig. 3, clauses and subclauses 1)
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add hexahydroaniline (144 microlitres, 1.26 mmoles), ethylene glycol (0.11 milliliter, 1.97 mmoles) and the solution of 4-iodoanisole (235 milligrams, 1.00 mmoles) in the 1-butanols.The Schlenk test tube was stirred 14 hours at 100 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, green-brown suspension reaches room temperature, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With colourless organic phase drying (sodium sulfate), concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-ethyl acetate 55: 1,15 milliliter of flow point).Flow point 9-17 provides 143 milligrams of (70% productive rate) white crystals shape products.
1H NMR (400MHz, CDCl 3): δ 6.79-6.72 (m, 2H), 6.60-6.53 (m, 2H), 3.74 (s, 3H), 3.22 (br s, 1H), 3.16 (tt, J=10.2,3.6Hz, 1H), 2.10-1.98 (m, 2H), 1.80-1.69 (m, 2H), 1.68-1.58 (m, 1H), 1.4o-1.04 (m, 5H). 13CNMR (100MHz, CDCl 3): δ 151.8,141.6,114.8,114.7,55.8,52.7,33.6,25.9,25.0.IR (neat, cm -1): 3388,1509,1239,1038,818. analysis of control C 13H 19NO:C, 76.06; H, 9.33.
Actual measurement: C, 76.00, H, 9.32.
5-(4-methoxyphenyl amino)-1-amylalcohol (Fig. 3, clauses and subclauses 2)
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-amino-1-amylalcohol (135 microlitres, 1.24 mmoles), ethylene glycol (0.11 milliliter, 1.97 mmoles) and the solution of 4-iodoanisole (235 milligrams, 1.00 mmoles) in 1-butanols (1.0 milliliters).The Schlenk test tube was stirred 14 hours at 100 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, yellowish brown suspension reaches room temperature, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With colourless organic phase drying (sodium sulfate), concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Ethyl acetate, 15 milliliters of flow points).Flow point 6-15 provides 177 milligrams of (85% productive rate) light tan oily products.
1H NMR(400MHz，CDCl 3)：δ6.80-6.74(m，2H)，6.60-6.54(m，2H)，3.74(s，3H)，3.65(t，J＝6.4Hz，2H)，3.07(t，J＝7.0Hz，2H)，2.5(br s，2H)，1.68-1.55(m，4H)，1.52-1.41(m，2H). 13C NMR(100MHz，CDCl 3)：δ151.9，142.6，114.8，114.0，62.7，55.8，44.9，32.4，29.4，23.3.IR(neat，cm -1)：3350，1511，1233，1036，820.
Analysis of control C 12H 19NO 2: C, 68.87; H, 9.15. actual measurement: C, 68.93; H, 9.12.
N-(3-aminomethyl phenyl)-2-(1-cyclohexenyl) ethamine (Fig. 3, clauses and subclauses 3)
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 3-toluene iodide (130 microlitres, 1.01 mmoles), 2-(1-cyclohexenyl) ethamine (170 microlitres, 1.22 mmoles), ethylene glycol (115 microlitres, 1.97 mmoles), and Virahol (1.0 milliliters).The Schlenk test tube was stirred 22 hours at 80 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, green-brown suspension reaches room temperature, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With organic phase drying (sodium sulfate), concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-ethyl acetate 5 50: 1,15 milliliter of flow point).Flow point 12-17 provides 189 milligrams of oily products that (87% productive rate) is colourless.
1H NMR (400MHz, CDCl 3): δ 7.06 (t, J=7.4Hz, 1H), 6.52 (d, J=7.4Hz, 1H), 6.46-6.39 (m, 2H), 5.53 (m, 1H), 3.57 (br s, 1H), 3.14 (t, J=6.8Hz, 2H), 2.30-2.22 (m, 5H), and 2.07-1.98 (m, 2H), 1.97-1.90 (m, 2H), 1.67-1.52 (m, 4H). 13C NMR (100MHz, CDCl 3): δ 148.5,138.9,134.9,129.1,123.5,118.1,113.6,109.9,41.4,37.6,27.8,25.2,22.8,22.4,21.6.IR (neat, cm -1): 3406,1603,1590,1509,1492,1478,1328,766,691. analysis of control C 15H 21N:C, 83.67; H, 9.83. actual measurement: C, 83.82; H, 9.84.
2-(4-aminophenyl)-N-(3, the 5-3,5-dimethylphenyl) ethamine (Fig. 4, clauses and subclauses 4)
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), 2-(4-aminophenyl) ethamine (160 microlitres, 1.21 mmoles), ethylene glycol (115 microlitres, 2.06 mmoles), and Virahol (1.0 milliliters).The Schlenk test tube was stirred 22 hours at 80 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, ash-brown suspension reaches room temperature, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With the organic phase drying (sodium sulfate) of Huang-brown, concentrate, dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-ethyl acetate 3: 2,15 milliliters of flow points).Concentrate flow point 9-18, resistates obtains the required product of white needle shape of 167 milligrams (69% productive rates) with hexane (5 milliliters) recrystallization.
1H NMR(400MHz，CDCl 3)：δ7.04-6.97(m，2H)，6.67-6.61(m，2H)，6.36(s，1H)，6.24(s，2H)，3.65-3.50(br m，3H)，3.30(t，J＝6.8Hz，2H)，2.79(t，J＝7.0Hz，2H)，2.23(s，6H). 13C NMR(100MHz，CDCl 3)：δ148.2，144.7，138.8，129.5，129.2，119.3，115.3，110.9，45.3，34.6，21.5.IR(neat，cm -1)：3361，3215，1600，1515，1472，1337，1273，1181，820.
N-(4-aminomethyl phenyl)-N '-3-(4-aminomethyl phenyl amino) propyl group]-1,4-butanediamine (Fig. 3, clauses and subclauses 6)
The cuprous iodide (9.6 milligrams, 0.0504 mmole) of in 15 milliliters of Schlenk pipes that can seal again of drying, packing into, 4-toluene iodide (260 milligrams, 1.19 mmoles), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add N-(3-aminopropyl)-1,4-butanediamine (79 microlitres, 0.503 mmole), ethylene glycol (115 microlitres, 2.06 mmoles), and Virahol (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 80 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, ash-brown suspension reaches room temperature, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With organic phase drying (sodium sulfate), concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; The saturated methylene chloride-methanol of methylene dichloride-30% aqueous ammonia 30: 20: 2,15 milliliters of flow points).Concentrate flow point 12-24, resistates obtains the required product of fine white crystals shape of 119 milligrams (673% productive rates) with hexane (2 milliliters) recrystallization.
1H NMR (400MHz, CDCl 3): δ 6.98 (d, J=8.4Hz, 4H), 6.56-6.50 (m, 4H), 4.04 (br s, 1H), 3.56 (br s, 1H), 3.17 (t, J=6.6Hz, 2H), 3.11 (t, J=6.6Hz, 2H), 2.74 (t, J=6.6Hz, 2H) 2.64 (t, J=6.9Hz, 2H), 2.23 (s, 6H), 1.79 (quintet, J=6.6Hz, 2H), 1.70-1.54 (m, 4H), 0.95 (br s, 1H). 13C NMR (100MHz, CDCl 3): δ 146.3,146.1,129.7,126.3,112.89,112.85,49.8,48.5,44.2,43.3,29.6,27.8,27.3,20.4.
Embodiment 79
Use the 2-phenylphenol to prepare N-phenyl hexylamine as solvent as ligand and toluene
Figure A20061008248101681
Wash down the nut test tube with nitrogen, the cuprous iodide of packing into (9.5 milligrams, 0.0499,5.0mol%) the 2-phenylphenol (34 milligrams, 0.200 mmole, 20mol%) and K 3PO 4(440 milligrams, 2.07 mmoles).Test tube lid lid is sent into the glove box that fills nitrogen, removes lid before finding time immediately.With the silicone rubber septum that studs with ptfe surface test tube is sealed, remove from glove box then.Use syringe to add bromobenzene (105 microlitres, 1.00 mmoles), normal hexyl Amine (160 microlitres, 1.21 mmoles), and toluene (1.0 milliliters).Reaction mixture makes gained brown suspension reach room temperature after 100 ℃ of magnetic stir 23 hours, pours the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 15 milliliters of dichloromethane extractions.With the organic phase drying (sodium sulfate) of light brown, concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-methylene dichloride 2: 1,15 milliliters of flow points).Flow point 14-25 provides 112 milligrams of liquid required products that (63% productive rate) is colourless. 1H NMR spectrum is consistent with report.Barluenga，J.；Fananas，F.J.；Villamana，J.；Yus，M.J.Org.Chem.1982，47，1560.
Embodiment 80
Use the 2-phenylphenol to prepare N-phenyl hexylamine as solvent as ligand and dioxane
Wash down the nut test tube with nitrogen, the cuprous iodide of packing into (9.5 milligrams, 0.0499mmol, 5.0mol%) the 2-phenylphenol (34 milligrams, 0.200 mmole, 20mol%) and K 3PO 4(440 milligrams, 2.07 mmoles).Test tube lid lid is sent into the glove box that fills nitrogen, removes lid before finding time immediately.With the silicone rubber septum that studs with ptfe surface test tube is sealed, remove from glove box then.Use syringe to add bromobenzene (105 microlitres, 1.00 mmoles), normal hexyl Amine (160 microlitres, 1.21 mmoles), and dioxane (1.0 milliliters).After 100 ℃ of magnetic stir 23 hours, make gained brown suspension reach room temperature reaction mixture, use the dilution of ether (2 milliliters) and water (1 milliliter) then.Add dodecane (230 microlitres; Mark in the GC), analyze demonstration by GC, top layer (organic layer) bromobenzene transformation efficiency is 74%, and the productive rate of required product is 60%.
Embodiment 81
Use 2-phenylphenol is as ligand and do not having preparation N-phenyl hexylamine under the situation of solvent
Wash down the nut test tube with nitrogen, the cuprous iodide of packing into (9.5 milligrams, 0.0499mmol, 5.0mol%) the 2-phenylphenol (34 milligrams, 0.200 mmole, 20mol%) and K 3PO 4(440 milligrams, 2.07 mmoles).Test tube lid lid is sent into the glove box that fills nitrogen, removes lid before finding time immediately.With the silicone rubber septum that studs with ptfe surface test tube is sealed, remove from glove box then.Use syringe to add bromobenzene (105 microlitres, 1.00 mmoles) and normal hexyl Amine (0.94 milliliter, 7.12 mmoles).After 100 ℃ of magnetic stir 23 hours, make gained brown suspension reach room temperature this reaction mixture, pour in the solution of (20 milliliters) of 30% ammonia (1 milliliter) in water, with 3 * 15 milliliters of dichloromethane extractions.With the organic phase drying (sodium sulfate) of light brown, concentrate, dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane-methylene dichloride 2: 1,15 milliliters of flow points).Flow point 13-25 provides 161 milligrams of liquid required products that (91% productive rate) is colourless. 1H NMR spectrum is consistent with report.Barluenga，J.；Fananas，F.J.；Villamana，J.；Yus，M.J.Org.Chem.1982，47，1560.
Embodiment 82
Prepare N-phenyl hexylamine with the phenyl trifluoromethanesulfonate methanesulfonates
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (19.5 milligrams, 0.102 mmole, 10mol%), the 2-phenylphenol (86 milligrams, 0.505 mmole, 50mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add normal hexyl Amine (135 microlitres, 1.02 mmoles) and phenyl trifluoromethanesulfonate methanesulfonates (0.98 milliliter, 6.05 mmoles).The Schlenk test tube was stirred 23 hours at 120 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained heavy-gravity, brown suspension reaches room temperature, uses ethyl acetate (2 milliliters) dilution then.Add dodecane (230 microlitres; Mark in the GC), by GC analytically the sample in the clear liquid show that the productive rate of required product is 1%.Confirm the characteristic (signal is at 177m/z) of this product by GC-MS.
Embodiment 83
Prepare N-(4-aminomethyl phenyl) hexylamine with the 4-toluene(mono)chloride
Figure A20061008248101691
In 15 milliliters of Schlenk pipes that can seal again of drying, pack into cuprous iodide (19.5 milligrams, 0.102 mmole, 10mol%), orthoxenol (86 milligrams, 0.505 mmole, 50mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add normal hexyl Amine (135 microlitres, 1.02 mmoles) and 4-toluene(mono)chloride (0.95 milliliter, 8.01 mmoles).The Schlenk test tube was stirred 23 hours at 120 ℃ of magnetic with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained brown suspension reach room temperature, and filter, with methylene dichloride (10 milliliters) wash-out by 0.5 * 1 centimetre of silica gel plug.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-methylene dichloride 2: 1; 15 milliliters of flow points).Concentrate flow point 12-23,, dodge the formula chromatography with silica gel and be further purified (2 * 15 centimetres of resistatess; Hexane-ethyl acetate 20: 1; 15 milliliters of flow points).Flow point 9-15 provides 85 milligrams (44% productive rate) colourless required pure products of large-scale crystalloid. 1H and 13C NMR spectrum is consistent with report.Wolfe，J.P.；Buchwald，S.L.J.Org.Chem.1996，61，1133.
Embodiment 84
Use the 2-phenylphenol as ligand, preparation N-phenyl-N ' in toluene, N ', N ", N " tetramethyl guanidine
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), the 2-phenylphenol (34 milligrams, 0.200 mmole, 20mol%), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add phenyl-iodide (112 microlitres, 1.00 mmoles), N, N, N ', N '-tetramethyl guanidine (190 microlitres, 1.51 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make the light brown suspension of gained reach room temperature, filter by plug of celite then, use the methylene dichloride wash-out.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Methyl alcohol-methylene dichloride (30% aqueous ammonia is saturated) 1: 5,20 milliliters of flow points).Flow point 26-43 provides 159 milligrams of (83% productive rate) required products.
Embodiment 85
2-(N-benzyl) benzaminic acid
Figure A20061008248101702
The aryl bromide substrate
Cuprous iodide (I) (19 milligrams, 0.10 mmole) K packs in the test tube that tetrafluoroethylene barrier film spiral covers 3PO 4(636 milligrams, 3.00 mmoles) and 2-bromo-benzoic acid (201 milligrams, 1.00 mmoles).Test tube found time and with argon gas backfill three times.Add 1-butanols (1.0 milliliters), ethylene glycol (111 microlitres, 2.00 mmoles) and benzylamine (131 microlitres, 1.20 mmoles) by microsyringe.This reactant 100 ℃ of heating 48 hours, is obtained light blue suspension.After making the reaction mixture thing reach room temperature, adding entry and dilute hydrochloric acid (10%) is 3 up to the pH value.Add ether (2 milliliters) and analyze organic layer by tlc.Further by ether (4 * 10 milliliters) extractive reaction mixture, with the organic phase that merges with the salt water washing and use dried over sodium sulfate.Silica gel column chromatography with ether/ethyl acetate=1/1 wash-out, obtains faint yellow solid shape 2-(N-benzyl) benzaminic acid (120 milligrams, 53% isolated yield).
The aryl chloride substrate
Use cuprous iodide (I) (19 milligrams, 0.10 mmole), K 3PO 4(636 milligrams, 3.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-chloro-benzoic acid (157 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 1-butanols (1.0 milliliters) and 100 ℃ the heating 72 hours.Continue to use aforesaid method, obtain faint yellow solid shape 2-(N-benzyl) benzaminic acid (109 milligrams, 48% isolated yield).
The aryl iodide substrate
Use cuprous iodide (I) (10 milligrams, 0.05 mmole), K 3PO 4(636 milligrams, 3.00 mmoles), benzylamine (131 microlitres, 1.20 mmoles), 2-iodo-benzoic acid (248 milligrams, 1.00 mmoles), ethylene glycol (111 microlitres, 2.00 mmoles) and 2-propyl alcohol (1.0 milliliters) and 80 ℃ the heating 18 hours.Continue to use aforesaid method, obtain faint yellow solid shape 2-(N-benzyl) benzaminic acid (161 milligrams, 71% isolated yield).
Embodiment 86
Under argon atmospher in toluene the general method of amination bromobenzene
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%) and anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and substituted phenol (0.2 mmole, 20mol%).This test tube found time and with argon gas backfill (3 times).At room temperature add dry toluene (1.0 milliliters), bromobenzene (105 microlitres, 1.0 mmoles) and normal hexyl Amine (158 microlitres, 1.2 mmoles) by micro-syringe.With 100 ℃ of heating of this reaction mixture 18 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, measure N-phenyl hexylamine productive rate.Use the embodiment of aforesaid method to list in Fig. 4.
Embodiment 87
Use 2 to prepare N-phenyl hexylamine as solvent as ligand and DMF
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%), anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and 2 (24 milligrams, 0.2 mmole, 20mol%).This test tube found time and with argon gas backfill (3 times).At room temperature add dry DMF (1.0 milliliters), bromobenzene (105 microlitres, 1.0 mmoles) and normal hexyl Amine (158 microlitres, 1.2 mmoles) by micro-syringe.With 100 ℃ of heating of this reaction mixture 18 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, the productive rate of measuring N-phenyl hexylamine is 48%.
Embodiment 88
The use 2 is as ligand and do not having preparation N-phenyl hexylamine under the situation of solvent
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%), anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and 2 (24 milligrams, 0.2 mmole, 20mol%).This test tube found time and with argon gas backfill (3 times).At room temperature add bromobenzene (105 microlitres, 1.0 mmoles) and normal hexyl Amine (1.05 milliliters, 8.0 mmoles) by micro-syringe.With 100 ℃ of heating of this reaction mixture 18 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, the transformation efficiency of measuring bromobenzene phenyl hexylamine is 100%.With the further aqueous phase extracted of ether (4 * 10 milliliters).With the organic phase water that merges, dried over sodium sulfate is used in the salt water washing.Except that desolvating, by the purification by silica gel column chromatography resistates, wash-out obtains colorless oil N-phenyl hexylamine (152 milligrams, 86% isolated yield) with hexane/ethyl acetate=20/1 wash-out by rotary evaporation.
Embodiment 89
The method of amination bromobenzene under air atmosphere
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%), anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and 2-phenylphenol (34 milligrams, 0.2 mmole, 20mol%).Under air atmosphere, at room temperature, add dry toluene (1.0 milliliters), bromobenzene (105 microlitres, 1.0 mmoles) and normal hexyl Amine (158 microlitres, 1.2 mmoles) by micro-syringe.With 100 ℃ of heating of this reaction mixture 22 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, the productive rate of measuring N-phenyl hexylamine is 33%.
Embodiment 90
Under argon atmospher in toluene the method for amination aryl iodide
The phenyl-iodide substrate
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%), anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and 2 (24 milligrams, 0.2 mmole, 20mol%).This test tube found time and with argon gas backfill (3 times).At room temperature add phenyl-iodide (112 microlitres, 1.0 mmoles) and normal hexyl Amine (158 microlitres, 1.0 mmoles) by micro-syringe.With 80 ℃ of heating of this reaction mixture 18 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, the productive rate of measuring N-phenyl hexylamine is 41%.
2-iodoanisole substrate
In the test tube that tetrafluoroethylene barrier film spiral covers, pack into cuprous iodide (I) (10 milligrams, 0.05 mmole, 5mol%), anhydrous phosphoric acid potassium fine powder (425 milligrams, 2.0 mmoles) and 2 (24 milligrams, 0.2 mmole, 20mol%).This test tube found time and with argon gas backfill (3 times).At room temperature add 2-iodoanisole (130 microlitres, 1.0 mmoles) and normal hexyl Amine (158 microlitres, 1.0 mmoles) by micro-syringe.With 80 ℃ of heating of this reaction mixture 18 hours.Make reaction mixture reach room temperature then.Add ether (2 milliliters), water (2 milliliters) and dodecane (interior mark, 227 microlitres).Analyze organic layer by GC, the productive rate of measuring N-(2-p-methoxy-phenyl) hexylamine is 41%.
Embodiment 91
1-phenyl-2-(2-tolyl amino) ethanol
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (5.0 milligrams, 0.026 mmole, 2.6mol%), NaOH (83.0 milligrams, 2.08 mmoles), with rac-2-amino-1-phenylethyl alcohol (143 milligrams, 1.04 mmoles).Under argon atmospher, add 2-toluene iodide (159 microlitres, 1.25 mmoles) and Virahol (1.0 milliliters) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 48 hours at 90 ℃ of magnetic.Cooling gained homogeneous solution dilutes with 10 mL of saline then.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organism 0.1M NaOH (2 * 10 milliliters) washing, with salt solution (1 * 15 milliliter) washing, with dried over mgso and concentrated.By silica gel chromatography purifying crude product material, use the methylene dichloride wash-out.The product was obtained as a pale yellow，viscous oil in 92％yield(217.4mg).
Embodiment 92
Instead-2-phenyl amino hexalin
Figure A20061008248101741
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (5.0 milligrams, 0.026 mmole, 2.6mol%), NaOH (83.0 milligrams, 2.08 mmoles), with rac-2-amino-1-hexalin HCl (158 milligrams, 1.04 mmoles).Under argon atmospher, add phenyl-iodide (139 microlitres, 1.25 mmoles), methyl-sulphoxide (670 microlitre) and 9.45M NaOH (330 microlitres, 3.12 mmoles) stock solution by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 48 hours at 90 ℃ of magnetic.Cooling gained homogeneous solution dilutes with 10 mL of saline then.Change this reaction mixture over to separating funnel, with extracted with diethyl ether (3 * 10 milliliters).Organic extract liquid is washed with 3M HCl (3 * 10 milliliters).Acid extraction liquid is cooled off in ice bath, use saturated NaOH solution this solution that alkalizes.When the pH test paper showed that the pH value of solution becomes alkalescence, this solution becomes got opaque.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organic extract liquid salt water washing, use dried over mgso, and concentrate.Obtain a kind of lurid oil, it is placed under high vacuum spend the night.This oil solidifies under vacuum atmosphere, obtains 182.5 milligrams of (92% productive rate) pale solids, mp 57-58 ℃.
Embodiment 93
Instead-2-(2-chloro-phenyl-amino) hexalin
Figure A20061008248101751
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (5.0 milligrams, 0.026 mmole, 2.6mol%), NaOH (125 milligrams, 3.12 mmoles), with rac-2-amino-1-hexalin HCl (158 milligrams, 1.04 mmoles).Under argon atmospher, add 2-chloro-1-phenyl-iodide (152 microlitres, 1.25 mmoles) and Virahol (1.0 milliliters) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 48 hours at 90 ℃ of magnetic.Cooling gained homogeneous solution dilutes with 10 mL of saline then.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organism salt water washing, use dried over mgso, and concentrate.By silica gel chromatography purifying crude product material, use hexane/ethyl acetate (60: 40) wash-out.Obtain the yellow oil product of 91% productive rate (212.7 milligrams).
Embodiment 94
2-[ethyl-(2-methoxyphenyl) amino] ethanol
Figure A20061008248101752
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (5.0 milligrams, 0.02 6 mmole, 2.6mol%), and NaOH (83.0 milligrams, 2.08 mmoles).Under argon atmospher, add 2-(amino-ethyl)-ethanol (101 microlitres, 1.04 mmoles), 2-iodoanisole (162 microlitres, 1,25 mmole), and Virahol (1.0 milliliters) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 48 hours at 90 ℃ of magnetic.Cooling gained homogeneous solution dilutes with 10 mL of saline then.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters). with organism 0.1M NaOH (2 * 10 milliliters) washing, with salt solution (1 * 15 milliliter) washing, with dried over mgso and concentrated.By silica gel chromatography purifying crude product material, use dichloromethane/ethyl acetate (70: 30) wash-out.Obtain the light yellow of 72% productive rate (145.8 milligrams), viscosity oily product.
Embodiment 95
2-(3-nitrophenyl amino)-1-phenylethyl alcohol
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (5.0 milligrams, 0.026 mmole, 2.6mol%), K 3PO 4(425 milligrams, 2.0 mmoles), rac-2-amino-1-phenylethyl alcohol (140 milligrams, 1.02 mmoles) and 1-iodo-3-oil of mirbane (302 milligrams, 1.25 mmoles).Under argon atmospher, add ethylene glycol (56 microlitres, 1.02 mmoles) and Virahol (1.0 milliliters) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 48 hours at 75 ℃ of magnetic.Reaction mixture is then with 10 mL of saline dilutions and with dichloromethane extraction (3 * 10 milliliters).With organic extract liquid 0.1M NaOH (2 * 10 milliliters) washing, with salt solution (1 * 15 milliliter) washing, with dried over mgso and concentrated.By silica gel chromatography purifying crude product material, use dichloromethane/ethyl acetate (96: 4) wash-out.Obtain the orange of 66% productive rate (172.8 milligrams), viscosity oily product.
Embodiment 96
N-phenyl ephedrine
Figure A20061008248101762
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (10.0 milligrams, 0.052 mmole, 5.2mol%), NaOtBu (288 milligrams, 3.0 mmoles) and (1R, 2S)-racephedrine HCl (202 milligrams, 1.0 mmoles).Under argon atmospher, add phenyl-iodide (168 microlitres, 1.5 mmoles) and methyl-sulphoxide (1.25 milliliters) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 22 hours at 100 ℃ of magnetic.Cooling gained solution dilutes with 10 mL of saline then.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organism 0.1M NaOH (2 * 10 milliliters) washing, with salt solution (1 * 15 milliliter) washing, with dried over mgso and concentrated.By silica gel chromatography purifying crude product material, use the methylene dichloride wash-out.Obtain the light yellow of 72% productive rate (175 milligrams), viscosity oily product.
1H NMR (500MHz, CDCl 3): 1.16 (d, J=6.9Hz, 3H), 2.39 (broad peak s, 1H), 2.70 (s, 3H), 4.01 (dq, J=6.9,5.5Hz, 1H), 4.74 (d, J=5.2Hz, 1H), 6.68 (m, 3H), 7.20 (m, 7H). 13C NMR (125MHz, CDCl 3): 12.1,32.4,59.5,75.9,113.3,116.8,125.9,127.3,128.1,129.0,142.5,150.0.
Embodiment 97
The preparation of O-phenyl ephedrine
Figure A20061008248101771
In 15 milliliters of screw capped tubes that the tetrafluoroethylene membrane cover is housed the back add cuprous iodide (10.0 milligrams, 0.05 mmole, 5mol%), Cs 2CO 3(652 milligrams, 2.00 mmoles) and (1R, 2S)-racephedrine HCl (165 milligrams, 1.00 mmoles).Add phenyl-iodide (168 microlitres, 1.50 mmoles) and butyronitrile (1 milliliter) in the time of with nitrogen purging.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 25.5 hours at 125 ℃ of magnetic.Cooling gained out-phase solution is then with 5 milliliters of ethyl acetate dilutions.Filter reaction mixture, removing desolvates obtains a kind of dark oil; This oil is changed in the small volume ether, be added to then among rare HCl.Vacuum filtration is collected the gained white precipitate and is used the hexane thorough washing.After the vacuum-drying, obtain the HCl salt of 67% productive rate (187.1 milligrams).All characterization data are all from free alkali.
1H NMR (300MHz, CDCl 3): δ 1.12 (d, J=6.3Hz, 3H), 1.34 (broad peak s, 1H), 2.43 (s, 3H), 2.92 (dq, J=6.6,4.4Hz, 1H), 5.17 (d, 1H), 6.83 (m, 3H), 7.22 (m, 7H). 13C NMR (75.5MHz, CDCl 3): 14.8,34.0,60.3,81.3,115.6,120.6,126.4,127.4,128.3,129.1,139.2,158.0.
Embodiment 98
Use sodium hydroxide in DMSO, to prepare benzylaniline as alkali
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (10.0 milligrams, 0.052 mmole, 5mol%).Add phenyl-iodide (116 microlitres, 1.04 mmoles), benzylamine (114 microlitres, 1.04 mmoles), methyl-sulphoxide (660 microlitre) and 6.33MNaOH (330 microlitres, 2.08 mmoles) by syringe.Use the argon purge test tube, replace membrane cover with solid polytetrafluor ethylene liner lid then.Reactant was stirred 4.25 hours at 110 ℃ of magnetic.Reaction mixture is then with 10 ml waters dilutions and with extracted with diethyl ether (3 * 10 milliliters).Organic extract liquid is washed with 3.0MHCl (3.0 * 10 milliliters).Acid extraction liquid is cooled off in ice bath, use saturated NaOH solution this solution that alkalizes.When the pH test paper showed that the pH value of solution becomes alkalescence, this solution becomes got opaque.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organic extract liquid salt water washing, use dried over mgso, and concentrate.Obtain the light yellow of 19% productive rate (35.9 milligrams), viscosity oily product.
Embodiment 99
Use sodium hydroxide in DMSO, to prepare N-phenylbenzyl amine as alkali, N-phenyl-N-methyl-benzyl amine, N-phenyl-(1-phenyl-ethyl amine) and N-Phenylpiperidine
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (10.0 milligrams, 0.052 mmole, 5mol%).Add phenyl-iodide (116 microlitres, 1.04 mmoles), amine (1.04 mmole), methyl-sulphoxide (660 microlitre) and 6.33M NaOH (330 microlitres, 2.08 mmoles) by syringe.Use the argon purge test tube, replace membrane cover with solid polytetrafluor ethylene liner lid then.Reactant was stirred 20.5 hours at 95 ℃ of magnetic.Reaction mixture is then with 5 ml waters and 5 milliliters of ether dilutions.Getting aliquots containig GC analyzes; The GC productive rate is respectively 26%, 6%, and 12% and 13%.
Embodiment 100
Use sodium hydroxide in DMSO, to make 5-amino-1-amylalcohol and 4-amino-1-butanols N-arylation as the alkali methyl-sulphoxide
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add then cuprous iodide (10.0 milligrams, 0.052 mmole, 5mol%).Add phenyl-iodide (116 microlitres, 1.04 mmoles), amino alcohol (1.04 mmole), methyl-sulphoxide (660 microlitre) and 6.33M NaOH (330 microlitres, 2.08 mmoles) by syringe.Use the argon purge test tube, replace membrane cover with solid polytetrafluor ethylene liner lid then.Reactant was stirred 24 hours at 90 ℃ of magnetic.Reaction mixture is then with 10 ml waters dilutions and with extracted with diethyl ether (3 * 10 milliliters).Organic extract liquid is washed with 3.0MHCl (3.0 * 10 milliliters).Acid extraction liquid is cooled off in ice bath, use saturated NaOH solution this solution that alkalizes.When the pH test paper showed that the pH value of solution becomes alkalescence, this solution becomes got opaque.Change this reaction mixture over to separating funnel, with dichloromethane extraction (3 * 10 milliliters).With organic extract liquid salt water washing, use dried over mgso, and concentrate.Obtain a kind of lurid oil, it is placed under high vacuum spend the night.Obtain faint yellow, thickness oily product; Isolated yield is respectively 49% and 47%.
Embodiment 101
Use sodium hydride in THF, to prepare 2-phenyl amino ethanol as alkali
With 15 milliliters of screw capped tube argon purge that the tetrafluoroethylene membrane cover is housed, add (10.0 milligrams of cuprous iodides then, 0.052 mmole, 5mol%), NaH (dispersion in 60% mineral oil, 25 milligrams, 1.04 mmoles), thanomin (63 microlitres, 1.04 mmoles) and tetrahydrofuran (THF) (1 milliliter).Reaction stirred is calmed down up to bubble.Add phenyl-iodide (116 microlitres, 1.04 mmoles) by syringe and use the argon purge test tube, replace barrier film with solid polytetrafluor ethylene liner lid then.Reactant was stirred 24 hours at 65 ℃ of magnetic.Reaction mixture is then with 10 ml waters dilutions and with extracted with diethyl ether (3 * 10 milliliters).With organic extract liquid salt water washing, use dried over mgso, and concentrate.By column chromatography purification crude product material, use hexane/ethyl acetate (25: 75) wash-out.Obtain the oily product of 52% productive rate
1HNMR (500MHz, CDCl 3): 2.54 (broad peak s, 1H), 3.24 (t, J=5.2Hz, 2H), 3.76 (t, J=5.2Hz, 2H), 4.00 (broad peak s, 1H), 6.62 (m, 2H), 6.73 (m, 1H), 7.17 (m, 2H). 13CNMR (125MHz, CDCl 3): 46.0,61.0,113.2,117.8,129.2,148.0.
Embodiment 102
Under solvent-free situation, use orthoxenol to prepare 1-butoxy-3 as ligand and cesium carbonate as alkali, 5-dimethylbenzene
Figure A20061008248101791
The propyl carbinol (1.37 milliliters, 15.0 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (150 microlitres, 1.04 mmoles), cuprous iodide (19.8 milligrams, 0.104 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles) and orthoxenol (88.5 milligrams, 0.520 mmole).Test tube seals with nut.Reaction mixture is stirred and heated 40 hours at 105 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (237 microlitres, 1.04 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.It is 64% that GC analyzes the productive rate that shows required product.By 1H NMR and GC-MS (178m/z signal) confirm the characteristic of this product.
1H NMR(400MHz，CDCl 3)：δ6.52(s，1H)，6.47(s，2H)，3.88(t，J＝6.5Hz，2H)，2.21(s，6H)，1.72-1.63(m，2H)，1.47-1.32(m，2H)，0.90(t，J＝7.4Hz， 3H).
Embodiment 103
Under solvent-free situation, use orthoxenol to prepare 1-butoxy-3 as ligand and potassiumphosphate as alkali, 5-dimethylbenzene
The propyl carbinol (1.37 milliliters, 15.0 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (150 microlitres, 1.04 mmoles), cuprous iodide (19.8 milligrams, 0.104 mmole), K 3PO 4(571 milligrams, 2.69 mmoles) and orthoxenol (88.5 milligrams, 0.520 mmole).Test tube seals with nut.Reaction mixture is stirred and heated 40 hours at 105C magnetic.Make reaction mixture reach room temperature then.Add dodecane (237 microlitres, 1.04 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 5% that GC analyzes the productive rate that shows required product.
Embodiment 104
Use various ligands to prepare 1-butoxy-3,5-dimethylbenzene
The propyl carbinol (573 microlitres, 6.26 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), ligand (0.500 mmole) and toluene (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 36 hours at 105 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.The productive rate of the required product of GC assay determination; The results are shown in following table.
Ligand The GC productive rate
Orthoxenol
81％
2 75％
The 2-isopropyl-phenol 65％
The 1-naphthols 43％
2-(dimethylamino) ethanol 46％
N, the N-N-methylsarcosine 73％
Methyliminodiacetic acid 28％
N,N,N 20％
Embodiment 105
Use all kinds of SOLVENTS to prepare 1-butoxy-3,5-dimethylbenzene
The propyl carbinol (573 microlitres, 6.26 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), orthoxenol (85.1 milligrams, 0.500 mmole) and solvent (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 36 hours at 90 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.The productive rate of the required product of GC assay determination; The results are shown in following table.
Solvent The GC productive rate
1, the 4-dioxane 46％
1, the 2-glycol dimethyl ether 42％
Triethylamine
55％
Embodiment 106
Under the situation of no ligand, use cesium carbonate to prepare 1-butoxy-3 as alkali and toluene as solvent, 5-dimethylbenzene
The propyl carbinol (1.25 milliliters, 13.7 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles) and toluene (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 42 hours at 105 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dioxane (227 microlitres, 1.00 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.It is 50% that GC analyzes the productive rate that shows required product.
Embodiment 107
Use 1, the 10-phenanthroline is as ligand, and cesium carbonate prepares 1-butoxy-3 as alkali and toluene as solvent, 5-dimethylbenzene
The propyl carbinol (183 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), 1,10-phenanthroline (90.1 milligrams, 0.500 mmole) and toluene (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 40 hours at 110 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.It is 83% that GC analyzes the productive rate that shows required product.
Embodiment 108
The 4-butoxy aniline
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 4-Iodoaniline (219mg, 1.0 mmoles), and propyl carbinol (1.0 milliliters).Stirred 23 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 10: 1), obtain 66 milligrams of (40% productive rate) reddish-brown oily title compounds.
Embodiment 109
2-butoxy toluene
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 2-toluene iodide (127 microlitres, 1.0 mmoles) and propyl carbinol (1.0 milliliters).Stirred 23 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane), obtain 159 milligrams of (97% productive rate) colorless oil title compounds.
Embodiment 110
Use the 5mol% cuprous iodide to prepare 3-butoxy phenylmethylether
In test tube, pack into cuprous iodide (10 milligrams, 0.050 mmole, 5mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 3-iodoanisole (119 microlitres, 1.0 mmoles) and propyl carbinol (1.0 milliliters).Stirred 20 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane), obtain 177 milligrams of (98% productive rate) light yellow oily title compounds.
Embodiment 111
3-butoxy pyridine
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(652 milligrams, 2.0 mmoles), 3-iodine pyridine (205 milligrams, 1.0 mmoles) and propyl carbinol (1.0 milliliters).Stirred 23 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 8: 1), obtain 125 milligrams of (83% productive rate) faint yellow oily title compounds.
Embodiment 112
4-isopropoxy phenylmethylether
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 4-iodoanisole (234 milligrams, 1.0 mmoles) and Virahol (1.0 milliliters).Stirred 23 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 20: 1), obtain 138 milligrams of (83% productive rate) colorless oil title compounds.
Embodiment 113
4-cyclopentyloxy phenylmethylether
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), the 5-methyl isophthalic acid, the 10-phenanthroline (39 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(652 milligrams, 2.0 mmoles), 4-iodoanisole (234 milligrams, 1.0 mmoles) and cyclopentanol (1.0 milliliters).Stirred 24 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 30: 1), obtain 128 milligrams of (67% productive rate) colorless oil title compounds.
Embodiment 114
3-oxyethyl group phenylmethylether
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 3-iodoanisole (119 microlitres, 1.0 mmoles) and ethanol (1.0 milliliters).Stirred 20 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 30: 1), obtain 142 milligrams of (93% productive rate) colorless oil title compounds.
Embodiment 115
2-anisole methyl alcohol
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(456 milligrams, 1.4 mmoles), 2-iodobenzene methyl alcohol (234 milligrams, 1.0 mmoles) and methyl alcohol (1.0 milliliters).Stirred 24 hours at 80 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 2: 1), obtain 122 milligrams of (88% productive rate) colorless oil title compounds.
Embodiment 116
3-butoxy benzonitrile
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), the 5-methyl isophthalic acid, the 10-phenanthroline (39 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(652 milligrams, 2.0 mmoles), and 3-iodine benzonitrile (229mg, 1.0mmol), propyl carbinol (366 microlitres, 4.0 mmoles) and toluene (1 milliliter).Stirred 28 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 30 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 30: 1), obtain 152 milligrams of (87% productive rate) colorless oil title compounds.
Embodiment 117
The 3-HOMOVERATRONITRILE
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1, the 10-phenanthroline (36 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(652 milligrams, 2.0 mmoles), 3-iodine benzonitrile (229 milligrams, 1.0 mmoles), methyl alcohol (162 μ l, 4.0mmol) and toluene (1 milliliter).Stirred 23 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 5: 1), obtain 111 milligrams of (84% productive rate) colorless oil title compounds.
Embodiment 118
Selectively prepare 4-phenoxy group-2-butanols with the 1,3 butylene glycol zone
The 1,3 butylene glycol (178 microlitres, 2.00 mmoles) of in a nut test tube, packing into, phenyl-iodide (112 microlitres, 1.00 mmoles), cuprous iodide (19.4 milligrams, 0.100 mmole), 5-methyl isophthalic acid, 10-phenanthroline (38.8 milligrams, 0.200 mmole), Cs 2CO 3(652 milligrams, 2.00 mmoles) and toluene (1.0 milliliters).Test tube seals with nut.Reaction mixture is stirred and heated 44 hours at 110 ℃ of magnetic.Make reaction mixture reach room temperature then.With short silica gel plug filter reaction mixture, use the methylene dichloride wash-out.Decompression is removed and is desolventized.Silica gel chromatography purifying (35 gram, pentane/ethyl acetate 5: 1) obtains the required product of 55% productive rate.
Embodiment 119
(R)-3-(1-phenyl ethoxy) phenylmethylether
Figure A20061008248101852
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), the 5-methyl isophthalic acid, the 10-phenanthroline (39 milligrams, 0.20 mmole, 20mol%), Cs 2CO 3(652 milligrams, 2.0 mmoles), 3-iodoanisole (119 microlitres, 1.0 mmoles), (R)-(+)-the 1-phenylethyl alcohol (205 microlitres, 1.7 mmoles,＞99%ee) and toluene (1.0 milliliters).Stirred 32 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 30: 1), obtain 173 milligrams of (76% productive rate, 98%ee) colorless oil title compounds.
Embodiment 120
Use low catalyst to load preparation 1-oxygen in heptan base-3,5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (4.75 milligrams, 0.025 mmole), 1,10-phenanthroline (1.80 milligrams, 0.01 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and o-Xylol (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 19 hours at 120 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; Interior mark) passes through diatomite filtration GC sample and use the methylene dichloride wash-out.It is 64% that GC analyzes the productive rate that shows required product.
Embodiment 121
Use all kinds of SOLVENTS to prepare 1-oxygen in heptan base-3, the general method of 5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (90.1 milligrams, 0.500 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and solvent (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 40 hours at 120 ℃ of magnetic.Make reaction mixture reach room temperature then.Dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.The productive rate of the required product of GC assay determination; The results are shown in following table.
Solvent The GC productive rate
DMF
52％
Three-n-propylamine 40％
The n-butyronitrile 62％
DMSO
41％
Embodiment 122
Use various nitrogen ligands to prepare 1-oxygen in heptan base-3, the general method of 5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), ligand (0.200 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and o-Xylol (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 19 hours at 120 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.The productive rate of the required product of GC assay determination; The results are shown in following table.
Ligand The GC productive rate
Oxine 30％
2-(aminomethyl) pyridine 28％
The 8-quinolylamine 6％
Embodiment 123
Use anti--N, N '-1, the 2-diamino-cyclohexane prepares 1-oxygen in heptan base-3,5-dimethylbenzene as ligand
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmole), cuprous iodide (19.0 milligrams, 0.100 mmole), anti--N, N '-dimethyl-1,2-diamino-cyclohexane (71.1 milligrams, 0.500 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and o-Xylol (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 17 hours at 140 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 67% that GC analyzes the productive rate that shows required product.
Embodiment 124
Use variously 1,10-phenanthroline type ligand prepares 1-oxygen in heptan base-3, the general method of 5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), ligand (0.200 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and toluene (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 39 hours at 110 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.The productive rate of the required product of GC assay determination; The results are shown in following table.
Ligand The GC productive rate
1, the 10-phenanthroline 81％
4,7-phenylbenzene-1,10-phenanthroline 91％
4,7-dimethyl-1,10-phenanthroline 85％
The 5-methyl isophthalic acid, the 10-phenanthroline 95％
5-chloro-1, the 10-phenanthroline 90％
5-nitro-1, the 10-phenanthroline 41％
Embodiment 125
At 70 ℃ of preparation 1-oxygen in heptan bases-3,5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmole), cuprous iodide (19.0 milligrams, 0.100 mmole), 5-methyl isophthalic acid, 10-phenanthroline (38.8 milligrams, 0.200 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and toluene (0.5 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 23 hours at 70 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 68% that GC analyzes the productive rate that shows required product.
Embodiment 126
Prepare 1-heptan oxygen base-3,5-dimethylbenzene with n-Heptyl alcohol as solvent at 70 ℃
The n-Heptyl alcohol (1.00 milliliters) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 5-methyl isophthalic acid, 10-phenanthroline (38.8 milligrams, 0.200 mmole) and Cs 2CO 3(977 milligrams, 3.00 mmoles).Test tube seals with nut.Reaction mixture is stirred and heated 48 hours at 70 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 100% that GC analyzes the productive rate that shows required product.
Embodiment 127
At room temperature prepare 1-oxygen in heptan base-3,5-dimethylbenzene as solvent with n-Heptyl alcohol
The n-Heptyl alcohol (1.00 milliliters) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (144 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 5-methyl isophthalic acid, 10-phenanthroline (38.8 milligrams, 0.200 mmole) and Cs 2CO 3(977 milligrams, 3.00 mmoles).Test tube seals with nut.With this reaction mixture magnetic stirring at room temperature 29 hours.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 18% that GC analyzes the productive rate that shows required product.
Embodiment 128
With 3, the 5-dimethyl bromobenzene prepares 1-oxygen in heptan base-3,5-dimethylbenzene
The n-Heptyl alcohol (283 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl phenyl-iodide (136 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (90.1 milligrams, 0.500 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and o-Xylol (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 44 hours at 140 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 16% that GC analyzes the productive rate that shows required product.
Embodiment 129
Use the 5-methyl isophthalic acid, the 10-phenanthroline as ligand by 2-bromobenzene ethanol preparation 2,3-Dihydrobenzofuranes
Figure A20061008248101891
The 2-bromobenzene ethanol of in a nut test tube, packing into (136 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 5-methyl isophthalic acid, 10-phenanthroline (38.8 milligrams, 0.200 mmole), Cs 2CO 3(977 milligrams, 3.00 mmoles), and toluene (1 milliliter).Test tube seals with nut.Reaction mixture is stirred and heated 43 hours at 110 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 72% that GC analyzes the productive rate that shows required product.
Embodiment 130
(R)-4-benzyl-3-phenyl-2- oxazolidone
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), (R)-4-benzyl-2- oxazolidone (215 milligrams, 1.21 mmoles), K 3PO 4(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add racemic anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 liters, 0.102 mmole, 10mol%), phenyl-iodide (106 microlitres, 0.947 mmole) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.The light blue suspension cool to room temperature of gained is filtered by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 11-19 provides 238 milligrams of required products of (99% productive rate) light tan solid state.HPLC on the Daicel OD post analyzes (hexane-Virahol 85: 15,0.7 ml/min, t r(R)=23.3 minute, t r(S)=26.7 minute) show＞99.5% ee.
Embodiment 131
Instead-N-(4-dimethylamino phenyl)-3-Phenyl Acrylamide
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), 4-dimethylamino-1-bromobenzene (201 milligrams, 1.00 mmoles), anti--cinnamide (178 milligrams, 1.21 mmoles), K 2CO 3(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.The golden yellow suspension cool to room temperature of gained is filtered by 0.5 * 1cm silicagel pad then, with 1: 1 wash-out of 10 milliliters of ethyl acetate-methylene dichloride.Concentrated filtrate, resistates are dissolved in 10 milliliters of methylene dichloride, dodge formula purification by chromatography (2 * 20 centimetres, ethyl acetate-methylene dichloride 1: 4,15 milliliters of flow points) with silica gel.Flow point 10-20 provides 261 milligrams of (98% productive rate) golden yellow solid state products.
Embodiment 132
At 60 ℃, preparation N-phenylacetamide in 4 hours
In one 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (10 milligrams, 0.0525mmol, 5.0mol%), ethanamide (170 milligrams, 2.88 mmoles), K 3PO 4((450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (17 microlitres, 0.108 mmole, 10mol%), phenyl-iodide (115 microlitres, 1.03 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 4 hours at 60 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Behind gained suspension cool to room temperature, add ethyl acetate (1 milliliter) and dodecane (mark in 235 microlitres, GC).It is 100% that GC analyzes the productive rate that shows required product.
Embodiment 133
The use quadrol at 80 ℃, prepared N, the N-diphenylformamide as ligand in 4 hours
Figure A20061008248101911
In one 15 milliliters the Schlenk pipe that can seal again, pack into cuprous iodide (9.8 milligrams, 0.0515 mmole, 5.0mol%), N-formyl radical aniline (150 milligrams, 1.24 mmoles), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add quadrol (7.0 microlitres, 0.105 mmole, 10mol%), phenyl-iodide (115 microlitres, 1.03 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 4 hours at 80 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained suspension cool to room temperature, filter by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 10-18 provides 188 milligrams of required products of (93% productive rate) white solid.
Embodiment 134
The use 1 at 80 ℃, prepared N, the N-diphenylformamide as ligand in 4 hours
In one 15 milliliters the Schlenk pipe that can seal again, pack into cuprous iodide (9.8 milligrams, 0.0515 mmole, 5.0mol%), N-formyl radical aniline (150 milligrams, 1.24 mmoles), K 3PO 4(450 milligrams, 2.12 mmoles) find time and the filling argon gas.Under argon atmospher, add 1 (9.0 microlitres, 0.106 mmole, 10mol%), phenyl-iodide (115 microlitres, 1.03 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 4 hours at 80 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Behind gained suspension cool to room temperature, add ethyl acetate (1 milliliter) and dodecane (mark in 235 microlitres, GC).It is 91% that GC analyzes the productive rate that shows required product.
Embodiment 135
N-formyl indole quinoline
Figure A20061008248101921
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), N-formyl-2-(2-bromophenyl) ethamine (229 milligrams, 1.00 mmoles), K 3PO 4(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.With gained suspension cool to room temperature, filter by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges formula purification by chromatography resistates (2 * 10 centimetres, hexane-ethyl acetate 3: 2,15 milliliters of flow points) with silica gel.Flow point 13-23 provides 145 milligrams of required products of (99% productive rate) light yellow solid shape.
Embodiment 136
At room temperature prepare N-formyl indole quinoline by aryl bromide
Except that be reflected at 25 ℃ carried out 24 hours, continue to use above method fully.Gained suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 1; 15 milliliters of flow points).Flow point 12-21 provides 107 milligrams of required products of (73% productive rate) light yellow solid shape.
Embodiment 137
Prepare N-formyl indole quinoline at 80 ℃ by aryl chloride
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), N-formyl-2-(2-chloro-phenyl-) ethamine (184 milligrams, 1.00 mmoles), K 2CO 3(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%) and toluene (1.0 milliliters).The Schlenk test tube was stirred 22 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.The light blue suspension cool to room temperature of gained is filtered by 0.5 * 1 centimetre of silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 1; 15 milliliters of flow points).Flow point 13-20 provides 105 milligrams of required products of (71% productive rate) white solid.
Embodiment 138
Use 2 to prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone as this ligand
Figure A20061008248101931
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), 2 (25 milligrams, 0.205 mmole, 20mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), 2-Pyrrolidone (95 microlitres, 1.25 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 21 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained suspension cool to room temperature, filter by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 13-24 provides 180 milligrams of required products of (95% productive rate) white solid.
Embodiment 139
Use normal hexyl Amine to prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidones at 80 ℃ as ligand/solvent
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), 2-Pyrrolidone (95 microlitres, 1.25 mmoles) and normal hexyl Amine (0.94 milliliter, 7.12 mmoles).The Schlenk test tube was stirred 23 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.With gained brown suspension cool to room temperature, filter by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 10 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 10 milliliters of flow points).Flow point 9-19 provides 185 milligrams of required products of (98% productive rate) light tan solid state.
Embodiment 140
Use 2, the 6-xylenol prepares N-(3, the 5-3,5-dimethylphenyl)-N-phenylacetamide as ligand
Figure A20061008248101941
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), 2 (25 milligrams, 0.205 mmole, 20mol%), Acetanilide (165 milligrams, 1.22 mmoles), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 21 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Gained suspension cool to room temperature is filtered by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 12-20 provides 133 milligrams of required products of (56% productive rate) yellow solid shape.
Embodiment 141
Use normal hexyl Amine to prepare N-(3, the 5-3,5-dimethylphenyl)-N-phenylacetamide as ligand and solvent
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), Acetanilide (165 milligrams, 1.22 mmoles), K 3PO 4(440 milligrams, 2.07 mmoles) find time and the filling argon gas.Under argon atmospher, add two normal hexyl Amines (145 microlitres, 1.00 mmoles) and normal hexyl Amine (0.94 milliliter, 7.12 mmoles) between 5-iodine.The Schlenk test tube was stirred 21 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained light yellow suspension cool to room temperature, filter by 0.5 * 1cm silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 12-20 provides 205 milligrams of required products of (86% productive rate) light yellow solid shape.
Embodiment 142
Use normal hexyl Amine to prepare N-methyl-phenyl acetanilide,Phenacetylaniline as ligand
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%) and K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add phenyl-iodide (112 microlitres, 1.00 mmoles), N-methylacetamide (0.46 milliliter, 6.00 mmoles) and normal hexyl Amine (0.53 milliliter, 4.01 mmoles).The Schlenk test tube was stirred 21 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained white suspension cool to room temperature, filter by 0.5 * 1 centimetre of silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 12-20 provides 136 milligrams of required products of (91% productive rate) light tan solid state.
Embodiment 143
Use uncle's dj butyl imino--three (pyrrolidone-base)-phosphorane to prepare N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone as alkali
Figure A20061008248101952
Packing in 15 milliliters of Schlenk pipes that can seal again, cuprous iodide (9.5 milligrams, 5.0mol%), find time and the filling argon gas by 0.0499 mmole.Under argon atmospher, add anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), 5-iodine m-xylene (145 microlitres, 1.00 mmoles), 2-Pyrrolidone (95 microlitres, 1.25 mmole), tertbutylimido-three (pyrrolidone-base) phosphorane (0.62 milliliter, 2.03 mmoles), and toluene (1.0 milliliters).The Schlenk test tube was stirred 21 hours at 90 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With the gained clarification, the brown solution cool to room temperature filters by 0.5 * 2 centimetre of silicagel pad, then with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 10-19 provides 180 milligrams of required products of (95% productive rate) white solid.
Embodiment 144
Use 1,8-diazabicyclo [5.4.0] 11 carbon-7-alkene (DBU) prepares N as alkali, the N-diphenylformamide
Figure A20061008248101961
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), N-formyl radical aniline (146 milligrams, 1.21 mmoles) is found time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), phenyl-iodide (112 microlitres, 1.00 mmoles), toluene (1.0 milliliters) and 1,8-diazabicyclo [5.4.0] 11 carbon-7-alkene (DBU, 0.45 milliliter, 3.01 mmoles).The Schlenk test tube was stirred 22 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Behind gained clear solution cool to room temperature, add ethyl acetate (2 milliliters), saturated aqueous ammonium chloride (2 milliliters) and dodecane (mark in 235 microlitres, GC).Top layer GC analyzes the productive rate of the required product of demonstration 12%, by GC-MS analysis confirmation (the M+ signal is at 197m/z).
Embodiment 145
Prepare N-(2-methyl isophthalic acid-propenyl)-2-Pyrrolidone with vinyl bromide
Figure A20061008248101962
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), K 2CO 3(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), 1-bromo-2-methacrylic (145 microlitres, 1.42 mmoles), 2-Pyrrolidone (76 microlitres, 1.00 mmoles), and toluene (1.0 milliliters).The Schlenk test tube was stirred 21 hours at 90 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With the light blue suspension cool to room temperature of gained, filter by 0.5 * 1 centimetre of silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges formula purification by chromatography resistates (2 * 10 centimetres, ethyl acetate, 10 milliliters of flow points) with silica gel.Flow point 10-24 provides 134 milligrams of required products of (96% productive rate) colourless liquid shape.
Embodiment 146
At room temperature prepare anti--N-(1-hexenyl) benzamide
Figure A20061008248101971
In 15 milliliters of Schlenk pipes, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), benzamide (145 milligrams, 1.20 mmoles), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), anti--1-iodo-1-hexene (143 microlitres, 1.00 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 25 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.T filters the light blue suspension cool to room temperature of gained then by 0.5 * 1 centimetre of silicagel pad, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate, resistates are dissolved in 5 milliliters of methylene dichloride, dodge formula purification by chromatography (2 * 15 centimetres, hexane-ethyl acetate, 15 milliliters of flow points) with silica gel.Flow point 12-19 provides 140 milligrams of required products of (69% productive rate) white needle shape.
Embodiment 147
N-(4-aminomethyl phenyl)-para toluene sulfonamide
Figure A20061008248101972
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.5 milligrams, 0.0499 mmole, 5.0mol%), 4-toluene iodide (218 milligrams, 1.00 mmoles), para toluene sulfonamide (205 milligrams, 1.20 mmoles), K 3PO 4(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%) and N, dinethylformamide (1 milliliter).The Schlenk test tube was stirred 19 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.The light brown suspension of gained is cooled to room temperature, pours the aqueous ammonium chloride solution of 20 milliliters of dilutions into, and with 3 * 15 milliliters of dichloromethane extractions.With colourless organic phase drying (sodium sulfate), concentrate, by silica gel dodge formula purification by chromatography resistates (2 * 15 centimetres, hexane-ethyl acetate 52: 1,15 milliliter of flow point).Flow point 9-16 provides 251 milligrams of required products of (96% productive rate) white crystals shape.
Embodiment 148
N-ethyl-N-phenyl-right-toluol sulfonamide
Figure A20061008248101981
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), N-ethyl-right-toluol sulfonamide (240 milligrams, 1.20 mmoles), K 2CO 3(280 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1, the 2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), phenyl-iodide (112 microlitres, 1.00 mmoles) and toluene (1 milliliter).The Schlenk test tube was stirred 23 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained brown suspension cool to room temperature, filter by 0.5 * 1 centimetre of silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 4: 1; 15 milliliters of flow points).Flow point 10-17 provides 244 milligrams of (89% productive rate) required products.
Embodiment 149
Use 1,8-diazabicyclo [5.4.0] 11 carbon-7-alkene (DBU) prepares N-phenyl-right-toluol sulfonamide as alkali
In 15 milliliters of Schlepk pipes that can seal again, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), right-toluol sulfonamide (205 milligrams, 1.20 mmoles) find time and the filling argon gas.Under argon atmospher, add anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.102 mmole, 10mol%), phenyl-iodide (112 microlitres, 1.00 mmoles), toluene (1.0 milliliters) and 1,8-diazabicyclo [5.4.0] 11 carbon-7-alkene (DBU, 0.45 milliliter, 3.01 mmoles).The Schlenk test tube was stirred 22 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.The gained clear solution is cooled to room temperature, pours 20 milliliters of aqueous ammonium chloride solutions into, and with 3 * 15 milliliters of dichloromethane extractions.With the organic phase drying (sodium sulfate) that merges, concentrate, by silica gel dodge formula purification by chromatography resistates (2 * 15 centimetres, hexane-ethyl acetate 53: 1,15 milliliter of flow point).Flow point 9-15 provides 60 milligrams of required products of (24% productive rate) white solid.
Embodiment 150
Use anti--N, N '-dimethyl-1, the 2-cyclohexane diamine is as ligand arylation N-H heterocyclic general method
At the flame-dried Schlenk test tube that can seal again, perhaps in the test tube that can seal again, add cuprous iodide (5mol%), heterogeneous ring compound (1.0 mmole) and alkali (2.1 mmole).This Schlenk test tube is fixed with rubber septum, found time twice and fill with argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) successively, aryl halide (1.2 mmole), anti--N, N-dimethyl-1, each solvent of 2-cyclohexane diamine (10-20mol%) (1ml).With reaction tube sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Concentrated filtrate by column chromatography gained resistates, obtains required product.
1-(2-aminophenyl) indoles
Figure A20061008248101991
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole 10mol%) and toluene (1.0 milliliters), makes indoles (0.117 gram, 1.00 mmole), obtain thick product with 2-bromaniline (0.206 gram, 1.20 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 5: 1) obtain 0.148 gram (71% productive rate) colorless oil product.
1HNMR(400MHz，CDCl 3)：δ7.64(m，1H)，7.18(m，6H)，6.82(m，2H)，6.64(m，，1H)，3.52(bs，2H).
At 80 ℃ of preparation 1-(2-aminophenyl) indoles
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes indoles (0.117 gram, 1.00 mmole) 80 ℃ of reactions, obtain thick product with 2-bromaniline (0.263 gram, 1.20 mmoles).Identify the sample of above-mentioned product by comparing (GC), and the GC productive rate is 92% for previous preparation.
1-phenyl tryptamines
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes tryptamines (0.160 gram, 1.00 mmole), obtain thick product with phenyl-iodide (134 microlitres, 1.20 mmoles) reaction.Column chromatography (2 * 15 centimetres, methylene dichloride (ammonia is saturated): methyl alcohol 50: 1) obtain 0.206 gram (87% productive rate) yellow oil product.
1H NMR(400MHz，CDCl 3)：δ7.65(m，1H)，7.55(m，1H)，7.47(m，4H)，7.31(m，1H)，7.18(m，3H)，3.06(t，J＝7Hz，2H)，2.94(t，J＝7Hz，2H)，1.40(bs，2H).
At 80 ℃ of preparation 1-(4-carbethoxy phenyl) indoles
Figure A20061008248102011
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2--cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes indoles (0.117 gram, 1.00 mmole) 80 ℃ of reactions, obtain thick product with ethyl-4-iodo-benzoic acid ester (0.331 gram, 1.20 mmoles).By relatively (GC) evaluation, above-mentioned product is the sample of previous preparation, and the GC productive rate is 96%.
Prepare 1-(2-pyridyl) indoles by the 2-chloropyridine
Figure A20061008248102012
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes indoles (0.117 gram, 1.00 mmole), obtain thick product with 2-chloropyridine (113 microlitres, 1.20 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 9: 1) obtain 0.194 gram (100% productive rate) yellow oil product.
1HNMR(400MHz，CDCl 3)：δ9.24(s，1H)，9.05(s，1H)，8.41(s，1H)，7.75(m，2H)，7.60(m，2H)，7.48(m，1H).
1-phenyl purine
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), Cs 2CO 3(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and dimethyl formamide (1.0 milliliters), makes purine (0.120 gram, 1.00 mmole), obtain thick product with phenyl-iodide (225 microlitres, 2.00 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 1: 2) obtain 0.136 gram (69% productive rate) white solid product.
1HNMR(400MHz，CDCl 3)：δ8.00(d，J＝0.9Hz，1H)，7.52(m，3H)，7.42(m，5H)，6.73(dd，J＝0.6Hz and J＝3.3Hz，1H)，7.60(m，2H)，7.48(m，1H).
1-(4-aminomethyl phenyl)-3-chlorine indazole
Figure A20061008248102021
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2--cyclohexane diamine (32 microlitres, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes 3-chlorine indazole (0.153 gram, 1.00 mmole), obtain thick product with 4-toluene bromide (148 microlitres, 1.20 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 50: 1) obtain 0.211 gram (87% productive rate) colorless oil product.
1HNMR(400MHz，CDCl 3)：δ7.70(d，J＝8.2Hz，1H)，7.63(d，J＝8.5Hz，1H)，7.52(m，2H)，7.43(m，1H)，7.24(d，J＝8.2Hz，2H)，7.22(m，1H)，2.38(s，3H).
1-phenyl-1,2, the 4-triazole
Figure A20061008248102022
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole 10mol%) and dimethyl formamide (1.0 milliliters), makes 1,2,4-triazole (0.069 gram, 1.00 mmoles) and phenyl-iodide (134 microlitres, 1.20 mmoles) reaction obtain thick product.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 3: 1) obtain 0.135 gram (93% productive rate) white solid product.
1HNMR(400MHz，CDCl 3)：δ8.58(s，1H)，8.10(s，1H)，7.66(m，2H)，7.47(m，2H)，7.37(m，1H).
1-phenyl benzotriazole
Figure A20061008248102031
Use general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole 10mol%) and dimethyl formamide (1.0 milliliters), makes benzotriazole (0.119 gram, 1.00 mmole), obtain thick product with phenyl-iodide (134 microlitres, 1.20 mmoles) reaction.Column chromatography (2 * 15 centimetres, hexane: ethyl acetate 9: 1) obtain 0.186 gram (95% productive rate) white solid product.
1HNMR(400MHz，CDCl 3)：δ8.17(m，1H)，7.78(m，3H)，7.62(m，2H)，7.55(m，2H)，7.42(m，1H).
Embodiment 151
Use N, N '-dimethyl-ethylenediamine prepares 1-(4-tolyl) indoles as ligand
The cuprous iodide (0.002 gram, 0.01 mmole) of in the flame-dried Schlenk pipe that can seal again, packing into, indoles (0.141 gram, 1.20 mmoles) and K 3PO 4(0.446 gram, 2.1 mmoles) find time this Schlenk test tube twice and the filling argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) successively, 4-toluene bromide (123 microlitres, 1.00 mmoles), N, N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole) and toluene (1 milliliter).With reaction tube sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Show relatively that with the material of confirming the GC productive rate of this product is 92%.
Embodiment 152
Use the N-methyl ethylenediamine to prepare 1-(4-tolyl) indoles as ligand
The cuprous iodide (0.002 gram, 0.01 mmole) of in the flame-dried Schlenk pipe that can seal again, packing into, indoles (0.141 gram, 1.20 mmoles) and K 3PO 4(0.446 gram, 2.1 mmoles) find time this Schlenk test tube twice and the filling argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) successively, 4-toluene bromide (123 microlitres, 1.00 mmoles), N-methyl ethylenediamine (9 microlitres, 0.10 mmole) and toluene (1 milliliter).With reaction tube sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Show relatively that with the material of confirming the GC productive rate of this product is 99%.
Embodiment 153
Preparation 1-Phenylindole in air
The cuprous iodide (0.002 gram, 0.01 mmole) of in the flame-dried Schlenk pipe that can seal again, packing into, indoles (0.117 gram, 1.00 mmoles) and K 3PO 4(0.446 gram, 2.1 mmoles).Rubber septum is installed, under air atmosphere, is added dodecane (45 microlitres, 0.20 mmole) successively, phenyl-iodide (134 microlitres, 1.20 mmoles), anti--N, N '-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole) and toluene (1 milliliter).With reaction tube sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Show relatively that with the material of confirming the GC productive rate of this product is one 82%.
Embodiment 154
Use various copper source to prepare the 1-Phenylindole
The copper source (0.050 mmole) of in the flame-dried Schlenk pipe that can seal again, packing into, indoles (0.117 gram, 1.00 mmoles) and K 3PO 4(0.446 gram, 2.1 mmoles).Rubber septum is installed, under argon gas stream, is added dodecane (45 microlitres, 0.20 mmole) successively, phenyl-iodide (134 microlitres, 1.20 mmoles), anti--N, N '-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole) and toluene (1 milliliter).With reaction tube sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.The GC productive rate of required product is listed as follows.
The copper source The GC productive rate of 1-Phenylindole
Cu(copper bronze) 99％
CuI
100％
CuCl2
100％
Cu(OAc) 2 100％
Cu(OMe) 2 98％
Embodiment 155
Use the general method of aryl iodide arylation malonic ester
Find time to be equipped with the Schlenk test tube of drying of magnetic stirring bar and tetrafluoroethylene stopcock in the time of heating, and under argon atmospher, cool off.The cuprous iodide (9.6 milligrams, 5.0 moles of %) of in this test tube, packing into, 2-xenol (17.1 milligrams, 10.0 moles of %), Cs 2CO 3(0.490 milligram, 1.50 mmoles), and aryl iodide (if going up solid, 1.0 mmoles).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.By volume (1.0 mmole) adds aryl iodide (if liquid), then adds diethyl malonate (304 microlitres, 2.00 mmoles) and anhydrous THF (1.0 milliliters).Under Ar Pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and sealed tube is placed in the oil bath of 110 ℃ of preheatings.After fixed time, make the reactant cool to room temperature, and between 20 milliliters of ethyl acetate and 10 milliliters of saturated ammonium chlorides (aq), distribute.With organic moiety drying (sodium sulfate), use diatomite filtration, and concentrate with rotatory evaporator.Oil by therefore the silica gel chromatography purifying obtains obtains alpha-aromatic malonic ester product.
Phenyl ethyl malonate
Colorless oil product (217 milligrams, 92%); 24 hours reaction times.
4-methoxyphenyl diethyl malonate
Obtain colorless oil product (227 milligrams, 87%); 30 hours reaction times.
4-chloro-phenyl-diethyl malonate
Obtain colorless oil product (265 milligrams, 97%); 24 hours reaction times.
1-naphthyl diethyl malonate
Obtain light yellow solid shape product (280 milligrams, 98%); 30 hours reaction times.
3-trifluoromethyl diethyl malonate
Obtain colorless oil product (267 milligrams, 88%); 24 hours reaction times.
2-cumyl diethyl malonate
Obtain light yellow oily product (238 milligrams, 86%); The 31 hours reaction times (10 moles of % cuprous iodides are used for reaction).
2,4-Dimethoxyphenyl diethyl malonate
Obtain tawny solid state product (269 milligrams, 91%); 30 hours reaction times.
3-carbethoxy phenyl diethyl malonate
Obtain colorless oil product (265 milligrams, 86%); 24 hours reaction times.
4-aminophenyl diethyl malonate
Obtain yellow oil product (200 milligrams, 79%); 30 hours reaction times.
4-hydroxyphenyl diethyl malonate
Obtain colorless solid shape product (191 milligrams, 73%); 30 hours reaction times (2.5 equivalent Cs 2CO 3Be used for reaction).
4-N-acetylamino phenyl ethyl malonate
Obtain colorless solid shape product (214 milligrams, 72%); The 30 hours reaction times (10 moles of % cuprous iodides are used for reaction).
3-nitrophenyl diethyl malonate
Obtain yellow oil product (240 milligrams, 85%); 24 hours reaction times.
3-cyano-phenyl diethyl malonate
Obtain colorless oil product (194 milligrams, 73%); 24 hours reaction times.
Embodiment 156
Use the general method of aryl bromide arylation malonic ester
Find time to be equipped with the Schlenk test tube of drying of magnetic stirring bar and tetrafluoroethylene stopcock in the time of heating, and under argon atmospher, cool off.The cuprous iodide (9.6 milligrams, 5.0 moles of %) of in this test tube, packing into, oxine (14.5 milligrams, 10.0 moles of %), and Cs 2CO 3(0.490 milligram, 1.50 mmoles).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.By volume (1.0 mmole) adds aryl iodide, then adds malonic ester (2.00 mmole) and anhydrous dioxane (1.0 milliliters).Under Ar Pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and sealed tube is placed in the oil bath of 110 ℃ of preheatings.After fixed time, make the reactant cool to room temperature, handle, between 20 milliliters of ethyl acetate and 10 milliliters of saturated ammonium chlorides (aq), distribute then with n-undecane (105.6 microlitres, 0.50 mmole).Analyze organic moiety by GC and/or GC-MS.The response factor that use obtains from previous separated product is measured the GC productive rate of product.
4-methoxyphenyl diethyl malonate
19.5 after hour, the GC productive rate is 43%.
4-trifluoromethyl diethyl malonate
20.5 after hour, remove the malonic ester product of decarboxylation, outside the 4-trifluoromethyl ethyl acetate, GC-MS demonstration aryl bromide is finished to the conversion of title compound.
Embodiment 157
Synthesizing of alpha-aromatic acetic ester
Figure A20061008248102071
Find time to be equipped with the Schlenk test tube of drying of magnetic stirring bar and tetrafluoroethylene stopcock in the time of heating, and under argon atmospher, cool off.The cuprous iodide (9.6 milligrams, 5.0 moles of %) of in this test tube, packing into, 1,10-phenanthroline (10.9 milligrams, 5.5 moles of %), Cs 2CO 3(0.490 milligram, 1.50 mmoles) and 4-iodoanisole (0.226 gram, 0.97 mmole).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.Add methyl aceto acetate (0.15 milliliter, 1.18 mmoles), then add anhydrous dioxane (1.0 milliliters).Under Ar Pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and sealed tube is placed in the oil bath of 110 ℃ of preheatings.After 24 hour time, make the reactant cool to room temperature, and between 20 milliliters of ethyl acetate and 10 milliliters of saturated ammonium chlorides (aq), distribute.With organic moiety drying (sodium sulfate), use diatomite filtration, and concentrate with rotatory evaporator.Oil by therefore the silica gel chromatography purifying obtains obtains colorless oil product 4-methoxyphenyl acetic acid ethyl ester (106 milligrams, 56%).
Embodiment 158
The arylation of ethyl cyanacetate
Figure A20061008248102081
Find time to be equipped with the Schlenk test tube of drying of magnetic stirring bar and tetrafluoroethylene stopcock in the time of heating, and under argon atmospher, cool off.The cuprous iodide (9.6 milligrams, 5.0 moles of %) of in this test tube, packing into, 1,10-phenanthroline (10.9 milligrams, 5.5 moles of %), Cs 2CO 3(0.490 milligram, 1.50 mmoles) and 4-iodoanisole (0.230 gram, 0.98 mmole).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.Add ethyl cyanacetate (0.13 milliliter, 1.22 mmoles), then add anhydrous dioxane (1.0 milliliters).Under Ar Pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and sealed tube is placed in the oil bath of 110 ℃ of preheatings.After fixed time, make the reactant cool to room temperature, and between 20 milliliters of ethyl acetate and 10 milliliters of saturated ammonium chlorides (aq), distribute.With organic moiety drying (sodium sulfate), use diatomite filtration, and concentrate with rotatory evaporator.Oil by therefore the silica gel chromatography purifying obtains obtains yellow oil product 4-methoxyphenyl ethyl cyanacetate (132 milligrams, 61%).
Embodiment 159
Use anti--N, N '-dimethyl-1, the 2-cyclohexane diamine is as ligand vinylation indoles
General method
In the test tube that can seal again, add a stirring rod, add cuprous iodide (5mol%), indoles (1.00 mmole) and alkali (2.1 mmole).This test tube is fixed with rubber septum, found time and fill twice with argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) successively, vinyl halide (1.2 mmole), anti--N, N '-dimethyl-1,2-cyclohexane diamine (10mol%) and toluene (1 milliliter).Replace barrier film with nut, (oil bath was stirred 24 hours down if desired) in the temperature that requires with this reactant.Make reaction mixture reach envrionment temperature,, shake, place several minutes, analyze the top layer sample by GC and GC/MS then with the dilution of 2-3 milliliter ethyl acetate.
1-(2-methylpropenyl) indoles
Figure A20061008248102091
Use aforesaid general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), instead-N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole, 10mol%) and toluene (1.0 milliliters) make indoles (0.117 gram, 1.00 mmoles) and 1-bromo-2-methacrylic (123 microlitres, 1.20, obtain the indoles (GC) that 45-50% transforms mmole) 80 ℃ of reactions; Use GC/MS to analyze the structure of determining this product.
1-(1-hexenyl) indoles
Figure A20061008248102092
Use aforesaid general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), instead-N, N '-dimethyl-1,2-cyclohexane diamine (16 microlitres, 0.10 mmole, 10mol%) and toluene (1.0 milliliters) make indoles (0.117 gram, 1.00 mmoles) and 1-iodo-1-hexene (171 microlitres, 1.20, obtain 42% indoles (GC) that transforms mmole) in the envrionment temperature reaction; Use GC/MS to analyze the structure of determining this product.
Embodiment 160
Use 2-(aminomethyl) pyridine or N, N-diethyl salicylic amide is as ligand arylation indoles
In the test tube that can seal again, add a stirring rod, add cuprous iodide (5mol%), indoles (1.00 mmole) and K 3PO 4(2.1 mmole).This test tube is fixed with rubber septum, found time and fill twice with argon gas.Under argon atmospher, add dodecane (45 microlitres, 0.20 mmole) successively, vinyl halide (1.2 mmole), ligand (20mol%) and toluene (1 milliliter).Replace barrier film with nut, this reactant was stirred 24 hours 110 ℃ (oil bath).Make reaction mixture reach envrionment temperature,, shake, place the several minutes clock with the dilution of 2-3 milliliter ethyl acetate.Then by GC with analysed the top layer material in GC/MS minute.
1-(2-aminomethyl phenyl) indoles
Use aforesaid general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), 2-(aminomethyl) pyridine (21 microlitres, 0.20 mmole, 20mol%) and toluene (1.0 milliliters), make indoles (0.117 gram, 1.00 mmoles) and 2 bromo toluene (144 microlitres, 1.20 reaction mmole) obtains 38% indoles (GC) that transforms.Determine the structure (35%GC productive rate) of product by the reliable material of GC.
1-(2-aminomethyl phenyl) indoles
Figure A20061008248102102
Use aforesaid general method, and the use cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4(2.1 mmole), N, N-diethyl salicylic amide (0.039 gram, 0.20 mmole 20mol%) and toluene (1.0 milliliters), makes indoles (0.117 gram, 1.00 mmole), obtain 42% indoles (GC) that transforms with 2 bromo toluene (144 microlitres, 1.20 mmoles) reaction.Determine the structure (40%GC productive rate) of product by the reliable material of GC.
Embodiment 161
By phenylcarbinol and E-1-iodine hexene prepare the E-1-benzyloxy oneself-1-alkene
The phenylcarbinol (207 microlitres, 2.00 mmoles) of in a nut test tube, packing into, E-iodine hexene (210 milligrams, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (36.0 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and toluene (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 14 hours at 80 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 10: 1), obtain 136 milligrams of (72% productive rate) colourless liquid shape title compounds.
Embodiment 162
Prepare 1-benzyloxy-2-methacrylic by phenylcarbinol and 1-bromo-2-methacrylic
Figure A20061008248102111
The phenylcarbinol (207 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 1-bromo-2-methacrylic (103 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (36.0 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and toluene (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 48 hours at 80 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 10: 1), obtain 81 milligrams of (50% productive rate) colorless oil title compounds.
Embodiment 163
Prepare E-1-undecane oxygen base-own-1-alkene by positive undecyl alcohol and E-1-iodine hexene
Figure A20061008248102112
The positive undecyl alcohol (415 microlitres, 2.00 mmoles) of in a nut test tube, packing into, E-iodine hexene (210 milligrams, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (36.0 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and toluene (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 36 hours at 100 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 2O: 1), obtain 141 milligrams of (55% productive rate) colourless liquid shape title compounds.
Embodiment 164
Prepare 1E by E-2-undecene-1-pure and mild E-1-iodine decene, 2E-1-last of the ten Heavenly stems-1-alkene oxygen base 11 carbon-2-alkene
Figure A20061008248102121
E-2-undecene-1-the alcohol (401 microlitres, 2.00 mmoles) of in a nut test tube, packing into, E-1-iodine decene (266 milligrams, 1.00 mmoles), (19.0 milligrams of cuprous iodides, 0.100 mmole), 3,4,7,8-tetramethyl--1,10-phenanthroline (47.3 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and toluene (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 24 hours at 80 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 100 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 100: 1), obtain 141 milligrams of (199 milligrams, 68% productive rate) colorless oil title compounds.
Embodiment 165
Prepare 1E by Z-2-hexen-1-ol and E-1-iodine decene, 2Z-1-oneself-2-alkene oxygen base last of the ten Heavenly stems-2-alkene
Figure A20061008248102122
The Z-2-hexen-1-ol (237 microlitres, 2.00 mmoles) of in a nut test tube, packing into, E-1-iodine decene (266 milligrams, 1.00 mmoles), (19.0 milligrams of cuprous iodides, 0.100 mmole), 3,4,7,8-tetramethyl--1,10-phenanthroline (47.3 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and toluene (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 22 hours at 90 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 100: 1), obtain 135 milligrams of (57% productive rate) colorless oil title compounds.
Embodiment 166
By E-2-undecene-1-pure and mild E-1-iodine decene preparation 2,3-dioctyl-penta-4-enol
E-2-undecene-1-the alcohol (401 microlitres, 2.00 mmoles) of in a nut test tube, packing into, E-1-iodine hexene (266 milligrams, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 1,10-phenanthroline (36.0 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and o-Xylol (500 microlitre).Test tube found time and with argon gas backfill (washing 10 minutes).Test tube seals with nut.Reaction mixture is stirred and heated 19 hours at 140 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 3: 1), obtain 188 milligrams of (64% productive rate) yellow oily title compounds.
Embodiment 167
By E-2-undecene-1-pure and mild 3, the 5-dimethyl bromobenzene prepares E-1,3-dimethyl-5-11 carbon-2-alkene oxygen base-benzene
E-2-undecene-1-the alcohol (401 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl bromobenzene (136 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 3,4,7,8-tetramethyl--1,10-phenanthroline (47.3 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and o-Xylol (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 48 hours at 120 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 10: 1), obtain 128 milligrams of (47% productive rate) colorless oil title compounds.
Embodiment 168
Prepare 1-oxygen in heptan base-3,5-dimethylbenzene by corresponding aryl bromide
Figure A20061008248102141
The n-Heptyl alcohol (1.0 milliliters) of in a nut test tube, packing into, 3,5-dimethyl bromobenzene (136 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 3,4,7,8-tetramethyl--1,10-phenanthroline (47.3 milligrams, 0.200 mmole) and Cs 2CO 3(977 milligrams, 3.00 mmoles).Test tube seals with nut.Reaction mixture is stirred and heated 28 hours at 110 ℃ of magnetic.Make reaction mixture reach room temperature then.Add dodecane (227 microlitres, 1.00 mmoles; In mark), by diatomite filtration GC sample and use the methylene dichloride wash-out.It is 51% that GC analyzes the productive rate that shows required product.
Embodiment 169
By phenylcarbinol and 3, the 5-dimethyl bromobenzene prepares 1-benzyloxy-3,5-dimethylbenzene
Figure A20061008248102142
The phenylcarbinol (207 microlitres, 2.00 mmoles) of in a nut test tube, packing into, 3,5-dimethyl bromobenzene (136 microlitres, 1.00 mmoles), cuprous iodide (19.0 milligrams, 0.100 mmole), 3,4,7,8-tetramethyl--1,10-phenanthroline (47.3 milligrams, 0.200 mmole), Cs 2CO 3(489 milligrams, 1.50 mmoles), and o-Xylol (500 microlitre).Test tube seals with nut.Reaction mixture is stirred and heated 48 hours at 120 ℃ of magnetic.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 10: 1), obtain 135 milligrams of (64% productive rate) colorless oil title compounds.
Embodiment 170
The 3-anisidine
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(456 milligrams, 1.4 mmoles, 1.4 equivalents), 3-Iodoaniline (120 microlitres, 1.0 mmoles, 1.0 equivalents) and methyl alcohol (1.0 milliliters, 25 mmoles, 25 equivalents).Stirred 21 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 2: 1), obtain 96 milligrams of known title compounds of (78% productive rate) yellow oily.
Embodiment 171
3-isopropoxy pyridine
Figure A20061008248102151
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(652 milligrams, 2.0 mmoles, 2.0 equivalents), 3-iodine pyridine (205 milligrams, 1.0 mmoles, 1.0 equivalents) and Virahol propyl alcohol (1.0 milliliters, 13 mmoles, 13 equivalents).Stirred 21 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 4: 1), obtain 126 milligrams of (92% productive rate) colorless oil title compounds.
Embodiment 172
4-(anti--but-2-ene oxygen base) phenylmethylether
Figure A20061008248102152
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(652 milligrams, 2.0 mmoles, 2.0 equivalents), 4-iodoanisole (234 milligrams, 1.0 mmoles, 1.0 equivalents), anti--2-butylene-1-alcohol (171 microlitres, 2.0 mmoles, 2.0 equivalents) and toluene (0.5 milliliter).Stirred 22 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 30: 1), obtain 153 milligrams of (86% productive rate) faint yellow oily title compounds.
Embodiment 173
4-(2-methyl allyloxy) phenylmethylether
Figure A20061008248102161
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(652 milligrams, 2.0 mmoles, 2.0 equivalents), 4-iodoanisole (234 milligrams, 1.0 mmoles, 1.0 equivalents), methallyl alcohol (168 microlitres, 2.0 mmoles, 2.0 equivalents) and toluene (0.5 milliliter).Stirred 28 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 30: 1), obtain 139 milligrams of (78% productive rate) colorless solid shape title compounds.
Embodiment 174
4-(1-methyl allyloxy) phenylmethylether
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(652 milligrams, 2.0 mmoles, 2.0 equivalents), 4-iodoanisole (234 milligrams, 1.0 mmoles, 1.0 equivalents), 3-butene-2-alcohol (180 microlitres, 2.0 mmoles, 2.0 equivalents) and toluene (0.5 milliliter).Stirred 38 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 30: 1), obtain 96 milligrams of (54% productive rate) colorless oil title compounds.
Embodiment 175
The 2-[(4-methoxy propoxy) methyl] pyridine
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(652 milligrams, 2.0 mmoles, 2.0 equivalents), 4-iodoanisole (234 milligrams, 1.0 mmoles, 1.0 equivalents), 2-pyridyl methyl alcohol (193 microlitres, 2.0 mmoles, 2.0 equivalents) and toluene (0.5 milliliter).Stirred 22 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 1: 1), obtain 120 milligrams of (56% productive rate) faint yellow solid shape title compounds.
Embodiment 176
1-bromo-2-benzyloxy benzene
Figure A20061008248102172
In test tube, pack into cuprous iodide (20 milligrams, 0.10 mmole, 10mol%), 1,10-phenanthroline (36 milligrams, 0.20 mmole, 0.20 equivalent), Cs 2CO 3(456 milligrams, 1.4 mmoles, 1.4 equivalents), phenylcarbinol (207 microlitres, 2.0 mmoles, 2.0 equivalents), 2-bromine phenyl-iodide (128 microlitres, 1.0 mmoles, 1.0 equivalents) and toluene (0.5 milliliter).Stirred 36 hours at 110 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the methylene dichloride wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/methylene dichloride 2: 1), obtain 187 milligrams of (71% productive rate) colorless oil title compounds.
Embodiment 177
Use potassium 4-cyano group 2,6-di-t-butyl propoxy-potassium prepares N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone as alkali
Figure A20061008248102173
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), 4-cyano group-2,6-di-t-butyl propoxy-potassium (325 milligrams, 1.21 mmoles) is found time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained suspension cool to room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows required product by GC is 95%.
Embodiment 178
Use the 4-Dimethylamino pyridine as ligand, sodium tert-butoxide prepares N-(3, the 5-3,5-dimethylphenyl)-N-ethyl acetamide as alkali and N-N-methyl-2-2-pyrrolidone N-as solvent
Figure A20061008248102181
The cuprous iodide (190 milligrams, 1.00 mmoles) of in a Schlenk pipe, packing into, 4-Dimethylamino pyridine (245 milligrams, 2.01 mmoles), sodium tert-butoxide (115 milligrams, 1.20 mmoles) is found time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.0 mmoles), N-ethyl acetamide (142 microlitres, 1.51 mmoles) and N-N-methyl-2-2-pyrrolidone N-(1.0 milliliters).The Schlenk test tube was stirred 25 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained brown suspension reach room temperature, pour the solution of 30% ammonia (2 milliliters) in water (20 milliliters) into, with methylene dichloride (3 * 15 milliliters) extraction.Concentrate with the organic phase drying (sodium sulfate) of merging and by rotary evaporation.Thick product dodges (2 * 15 centimetres of formula purification by chromatography with silica gel; Hexane-ethyl acetate 3: 2; 15 milliliters of flow points).Flow point 8-16 provides 164 milligrams of (86% productive rate) white solid products.
Embodiment 179
Use two (1-Methylimidazole-2-yl) ketone to prepare N-(3, the 5-3,5-dimethylphenyl)-N-methylformamide as ligand
In 15 milliliters of Schlenk pipes that can seal again, pack into cuprous iodide (9.6 milligrams, 0.0504 mmole, 5.0mol%), two (1-Methylimidazole-2-yl) ketone (19 milligrams, 0.100 mmole, 10mol%), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), N-methylformamide (72 microlitres, 1.23 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows required product by GC is 95%.
Embodiment 180
At room temperature use 1 is worked as water gaging and is prepared N-formyl indole quinoline by corresponding aryl bromide in 4 hours
Figure A20061008248102191
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), N-[-2-(2-bromophenyl) ethyl] methane amide (229 milligrams, 1.00 mmoles), Cs 2CO 3(500 milligrams, 1.53 mmoles) find time and the filling argon gas.Add N under argon atmospher, (10mol%), THF (1 milliliter) adds entry (18 microlitres, 1.0 mmoles) to N '-dimethyl-ethylenediamine at last for 11 microlitres, 0.10 mmole.The Schlenk test tube was stirred 4 hours at 25 ± 5 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Gained pale blue green suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with ethyl acetate (20 milliliters) wash-out.Concentrated filtrate dodges (2 * 10 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 3; 15 milliliters of flow points).Flow point 8-17 provides 147 milligrams of (100% productive rate) light yellow solid shape products.
Embodiment 181
At room temperature in 7 hours, use 1 normal water to prepare N-(3, the 5-3,5-dimethylphenyl) benzamide
Figure A20061008248102192
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), benzamide (146 milligrams, 1.21 mmoles), CS 2CO 3(500 milligrams, 1.53 mmoles) find time and the filling argon gas.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), and 5-iodine m-xylene (145 microlitres, 1.00 mmoles), tetrahydrofuran (THF) (1.0 milliliters) adds entry (18 microlitres, 1.0 mmoles) at last.The Schlenk test tube was stirred 7 hours at 25 ± 5 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.The gained white suspension is filtered by 0.5 * 1 centimetre of silicagel pad, with ethyl acetate (20 milliliters) wash-out.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 3: 1; 15 milliliters of flow points; Sample dissolves with 1 milliliter of methylene dichloride).Flow point 9-15 provides 223 milligrams of (99% productive rate) white crystals shape products.
Embodiment 182
Use placed in-line arylamideization-ring extension prepared in reaction 2,3,5,6-tetrahydrochysene-1H-benzo [b]-1,5-diaza limonene-4-ketone
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), 2-azepine etidine ketone (86 milligrams, 1.21 mmoles), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.103 mmole, 10mol%), 2-iodine benzyl amine (132 microlitres, 1.00 mmoles) and toluene (1 milliliter).Stirred 22 hours at 100 ℃ with the Schlenk seal of tube and with reaction mixture.Make gained suspension reach room temperature, pour the solution of 30% ammonia (1 milliliter) in water (20 milliliters) into, with 3 * 20 milliliters of dichloromethane extractions.With the organic layer drying (sodium sulfate) that merges, concentrate, dodge formula purification by chromatography resistates (2 * 15 centimetres, ethyl acetate-methyl alcohol 10: 1,15 milliliters of flow points) by silica gel.Flow point 10-20 provides 144 milligrams of required products of (82% productive rate) white solid.
Embodiment 183
N-benzyl-N-(4-sulphomethyl phenyl) methane amide
Figure A20061008248102211
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), 4-bromine sulfo-phenylmethylether (204 milligrams, 1.00 mmoles), N-benzyl methane amide (163 milligrams, 1.21 mmoles), K 2CO 3(280 milligrams, 2.12 mmoles) find time and the filling argon gas tout court.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With the filbert suspension cool to room temperature of gained, filter by 0.5 * 1 centimetre of silicagel pad then, with 10 milliliters of eluent ethyl acetates.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 2: 1; 15 milliliters of flow points).Flow point 9-19 provides 243 milligrams of (94% productive rate) white solid products.Mp：73-74℃。
Embodiment 184
Use DMF to prepare 2-hydroxy-n-Phenylpropionamide as solvent
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), racemic lactic amide (107 milligrams, 1.20 mmoles), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), phenyl-iodide (112 microlitres, 1.00 mmoles) and dimethyl formamide (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 60 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained purple-blue suspension cool to room temperature, filter by 0.5 * 1 centimetre of silicagel pad then, with 10: 1 methylene chloride-methanol (20 milliliters) wash-outs.Use the Rotary Evaporators concentrated filtrate, then find time to remove dimethyl formamide at 0.1 mmhg.Resistates dodges (2 * 20 centimetres of formula purification by chromatography with silica gel; Methylene chloride-methanol 25: 1; 15 milliliters of flow points).Flow point 10-16 provides 146 milligrams of (88% productive rate) light tan solid state products.
Embodiment 185
N-tertbutyloxycarbonyl-4-chloroaniline
Figure A20061008248102221
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), 4-bromo-1-chlorobenzene (192 milligrams, 1.00 mmoles), t-butyl carbamate (142 milligrams, 1.21 mmoles), K 2CO 3(280 milligrams, 2.03 mmoles) find time and the filling argon gas tout court.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%) and toluene (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With the light blue suspension cool to room temperature of gained, filter by 0.5 * 1 centimetre of silicagel pad then, with ethyl acetate (10 milliliters) wash-out.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 9: 1; 15 milliliters of flow points).Flow point 12-22 provides 178 milligrams of (78% productive rate) white crystals shape products.
Embodiment 186
N-(3-aminomethyl phenyl)-2-piperidone
Figure A20061008248102222
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), δ-Valerolactim (120 milligrams, 1.21 mmoles), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas tout court.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), 3-iodine benzyl amine (134 microlitres, 1.01 mmoles), and toluene (1.0 milliliters).The Schlenk test tube was stirred 18 hours at 100 ℃ with tetrafluoroethylene jam pot cover mouth and with reaction mixture.With gained light yellow suspension cool to room temperature, 30% ammoniacal liquor (1 milliliter) and water (10 milliliters) then.Extract this two-phase mixture with methylene dichloride (3 * 15 milliliters).With the organic phase drying (sodium sulfate) that merges, concentrate, dodge (2 * 15 centimetres of formula purification by chromatography resistatess by silica gel; Methylene dichloride (30% ammoniacal liquor is saturated)-methylene chloride-methanol 10: 10: 1; 15 milliliters of flow points).Flow point 14-19 provides 199 milligrams of (96% productive rate) light yellow oily products.
Embodiment 187
N-(3-hydroxymethyl phenyl)-2-Pyrrolidone
Figure A20061008248102231
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%) and K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon gas.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), 3-iodine benzyl alcohol (128 microlitres, 1.01 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 3 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.With gained white suspension cool to room temperature, filter by 0.5 * 1 centimetre of silicagel pad then, with 5: 1 ether-methyl alcohol (10 milliliters) wash-outs.Concentrated filtrate dodges (2 * 20 centimetres of formula purification by chromatography resistatess with silica gel; Methylene chloride-methanol 25: 1; 15 milliliters of flow points).Flow point 14-19 provides 180 milligrams of (93% productive rate) white solid products.Mp：120-121℃。
Embodiment 188
Prepare N-(3-methyl-2-butene base)-2-Pyrrolidone by vinyl bromide
In 15 milliliters of screw capped tubes of tetrafluoroethylene membrane cover are housed, pack into cuprous iodide (10.0 milligrams, 0.05 mmole, 5mol%) and K 2CO 3(276 milligrams, 2.00 mmoles).In the time of with nitrogen purging, add 2-Pyrrolidone (76 microlitres, 1.00 mmoles), 2-bromo-3-methyl-2-butene (116 microlitres by syringe, 1.00 mmole), N, N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10 moles of %), 1,4-dioxane (1 milliliter).Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 38 hours at 100 ℃ of magnetic.Cooling gained out-phase solution is then with 5 milliliters of ethyl acetate dilutions.Filter reaction mixture is a yellow oil with the solution concentration that obtains.By silica gel chromatography purifying crude product material, use methylene dichloride: ethyl acetate (80: 20) wash-out, the yellow oil product of separating iodo 69% productive rate (105.3 milligrams).
1HNMR(300MHz，CDCl 3)：1.60(d，J＝1.4Hz，3H)，1.74(s，3H)，1.79(dd，J＝1.3，1.1Hz，3H)，2.14(m，2H)，2.42(t，J＝8.1Hz，2H)，3.44(t，J＝6.8Hz，2H). 13C NMR(75.5MHz，CDCl 3)：14.9，18.5，19.4，19.5，30.9，47.5，124.9，129.0，173.2.
Embodiment 189
Prepare N-(3-methyl-2-butene base) benzamide by vinyl bromide
Figure A20061008248102241
In 15 milliliters of screw capped tubes that the tetrafluoroethylene membrane cover is housed the back add cuprous iodide (10.0 milligrams, 0.05 mmole, 5mol%), K 2CO 3(276 milligrams, 2.0 mmoles) and hexanaphthene carboxylic acid amides (127 milligrams, 1.00 mmoles).In the time of with nitrogen purging, add 2-bromo-3-methyl-2-butene (116 microlitres, 1.00 mmoles), N, N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10 moles of %), 1,4-dioxane (1 milliliter) by syringe.Replace membrane cover with a solid polytetrafluor ethylene liner lid, reactant was stirred 38 hours at 100 ℃ of magnetic.Cooling gained out-phase solution is then with 5 milliliters of ethyl acetate dilutions.Filter reaction mixture removes and desolvates, and obtains white solid.Use ethyl acetate: hexane (1: 1) recrystallization purifying crude product material; Obtain the white fiber shape lenticular product of 62% productive rate (121.7 milligrams).
1H NMR (300MHz, CDCl 3): 1.55 (m, 10H), 1.60 (s, 3H), 1.68 (s, 3H), 1.87 (s, 3H), 2.12 (m, 1H), 6.40 (broad peak s, 1H). 13C NMR (75.5MHz, CDCl 3): 17.5,19.5,19.7,25.8,29.7,29.9,45.7,124.0,124.4,174.1.
Embodiment 190
Prepare N '-(3, the 5-3,5-dimethylphenyl) benzhydrazide by aryl bromide
The neutralized verdigris (6 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), benzhydrazide (207 milligrams, 1.5 mmoles) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was heated 22 hours at 90 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and/or GC-MS.By ethyl acetate (4 * 10ml) further extractive reaction things.With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by the purification by silica gel column chromatography yellow residue, is used dichloromethane/ethyl acetate (20: 1) wash-out, obtains the required product of white solid (107 milligrams, 46% productive rate).Rf=0.5 (dichloromethane/ethyl acetate=20: 1).
Embodiment 191
N-butyl-N '-(3-methoxyphenyl) urea
The cuprous iodide (10 milligrams, 0.05 mmole, 0.05 equivalent) of in test tube, packing into, K 3PO 4(425 milligrams, 2.0 mmoles, 2.0 equivalents), N-Butylurea (232 milligrams, 2.0 mmoles, 2.0 equivalents) is full of argon gas.Under argon atmospher, add 3-iodoanisole (119 microlitres, 1.0 mmoles, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 0.10 equivalent), anhydrous toluene (1.0 milliliters).Stirred 24 hours at 110 ℃ of magnetic with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use the ether wash-out.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Pentane/ether 1: 2), obtain 188 milligrams of (85% productive rate) faint yellow oily title compounds.
Embodiment 192
N-(3-methoxyphenyl)-2-imidazolone
The cuprous iodide (40 milligrams, 0.20 mmole, 0.10 equivalent) of in test tube, packing into, K 3PO 4(850 milligrams, 2.0 mmoles, 2.0 equivalents), 2-imidazolone (2.58 grams, 30.0 mmoles, 15.0 equivalent), 3-iodoanisole (238 microlitres, 2.0 mmoles, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (44 microlitres, 0.40 mmole, 0.20 equivalent) and anhydrous DMF (4.0 milliliters).Stirred 7 hours at 120 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 1: 2), obtain 288 milligrams of (75% productive rate) faint yellow solid shape title compounds.
Embodiment 193
Use microwave radiation to prepare N-(3-methoxyphenyl)-2-imidazolone
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in the microwave test tube, packing into, K 3PO 4(425 milligrams, 2.0 mmoles, 2.0 equivalents), 2-imidazolone (1.29 grams, 15.0 mmoles, 15.0 equivalents), 3-iodoanisole (119 microlitres, 1.0 mmole, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (22 microlitres, 0.20 mmole, 0.20 equivalent) and anhydrous DMF (2.0 milliliters), be full of argon gas.Stirred 15 hours at 130 ℃ in microwave with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 1: 2), obtain 128 milligrams of (67% productive rate) white solid title compounds.
Embodiment 194
N-(3-methoxyphenyl)-N '-(3, the 5-3,5-dimethylphenyl)-2-imidazolone
Figure A20061008248102262
The cuprous iodide (20 milligrams, 0.10 mmole, 0.20 equivalent) of in the microwave test tube, packing into, K 3PO 4(212 milligrams, 1.0 mmoles, 2.0 equivalents), N-(3-methoxyphenyl)-2-imidazolone (96 milligrams, 0.5 mmole, 1.0 equivalents), 3,5-dimethyl phenyl-iodide (144 microlitres, 1.0 mmoles, 2.0 equivalent), N, N '-dimethyl-ethylenediamine (22 microlitres, 0.20 mmole, 0.40 equivalent) and anhydrous DMF (2.0 milliliters), be full of argon gas.Stirred 15 hours and stirred other 15 hours at 130 ℃ in microwave with this test tube sealing and with reaction mixture at 160 ℃.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 4: 1), obtain 134 milligrams of (91% productive rate) white solid title compounds.
Embodiment 195
N-benzyl-N '-phenylurea
Figure A20061008248102271
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, K 3PO 4(425 milligrams, 2.0 mmoles, 2.0 equivalents), N-Butylurea (225 milligrams, 1.5 mmoles, 1.5 equivalents) is full of argon gas.Under argon atmospher, add bromobenzene (105 microlitres, 1.0 mmoles, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (22 microlitres, 0.20 mmole, 0.20 equivalent), and anhydrous dioxane (1.0 milliliters).Stirred 25 hours at 80 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Solid residue is dissolved in～2 milliliters of DMF.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 3: 1), obtain 179 milligrams of (79% productive rate) white solid title compounds.
Embodiment 196
N-benzyl-N '-(3-aminophenyl) urea
Figure A20061008248102272
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, K 3PO 4(425 milligrams, 2.0 mmoles, 2.0 equivalents), benzylurea (225 milligrams, 1.5 mmoles, 1.5 equivalents), 3-bromine phenylmethylether (109 microlitres, 1.0 mmole, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (22 microlitres, 0.20 mmole, 0.20 equivalent) and anhydrous dioxane (1.0 milliliters), be full of nitrogen.Stirred 24 hours at 80 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Solid residue is dissolved in～2 milliliters of DMF.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 1: 2), obtain 185 milligrams of (77% productive rate) faint yellow solid shape title compounds.
Embodiment 197
N-benzyl-N '-(2-methoxyphenyl) urea
Figure A20061008248102281
The cuprous iodide (20 milligrams, 0.10 mmole, 0.10 equivalent) of in test tube, packing into, K 3PO 4(425 milligrams, 2.0 mmoles, 2.0 equivalents), benzylurea (225 milligrams, 1.5 mmoles, 15.0 equivalents), 2-bromine phenylmethylether (125 microlitres, 1.0 mmole, 1.0 equivalents), N, N '-dimethyl-ethylenediamine (22 microlitres, 0.20 mmole, 0.20 equivalent) and anhydrous dioxane (1.0 milliliters), be full of nitrogen.Stirred 26 hours at 80 ℃ with this test tube sealing and with reaction mixture.Filter with gained suspension cool to room temperature and by 0.5 * 1 centimetre of silicagel pad, use eluent ethyl acetate.Vacuum concentrated filtrate.Solid residue is dissolved in～2 milliliters of DMF.Dodge (2 * 20 centimetres of formula purification by chromatography resistatess by silica gel; Hexane/ethyl acetate 2: 1), obtain 172 milligrams of (67% productive rate) white solid title compounds.
Embodiment 198
(R)-N-(3, the 5-3,5-dimethylphenyl)-α-Jia Jibianji amine
Figure A20061008248102282
The neutralized verdigris (6 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) by syringe, (R)-α-Jia Jibianji amine (193 microlitres, 1.5 mmoles) and DMF (0.5 milliliter).This reaction mixture was stirred 30 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and/or GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by the purification by silica gel column chromatography yellow residue, is used hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (160 milligrams, 71% productive rate, 98%ee).Rf=0.4 (hexane/ethyl acetate=20: 1).HPLC condition: (post: Daciel OD; Flow velocity: 0.7 ml/min; UV lamp: 254 nanometers; Solvent systems: hexane/2-Virahol (9: 1); Retention time: 7.80 minutes).
Embodiment 199
Prepare 3-methoxyl group-N-hexyl aniline by the 3-chloroanisole
Figure A20061008248102291
The neutralized verdigris (6 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 3-chloroanisole (122 microlitres, 1.0 mmoles) and normal hexyl Amine (0.5 milliliter) by syringe as solvent.This reaction mixture was stirred 24 hours at 130 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC, obtain the transformation efficiency of 64% 3-chloroanisole and the GC productive rate of 40% required product.
Embodiment 200
Prepare 4-nitro-N-hexyl aniline by 1-chloro-4-oil of mirbane
Figure A20061008248102292
The neutralized verdigris (6 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), 1-chloro-4-oil of mirbane (158 milligrams, 1.0 mmoles) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 22 hours at 120 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by the purification by silica gel column chromatography orange residue, is used hexane/ethyl acetate (10: 1) wash-out, obtains the required product of yellow solid shape (199 milligrams, 90% productive rate).Rf=0.2 (hexane/ethyl acetate=10: 1).
Embodiment 201
Prepare N-(3, the 5-3,5-dimethylphenyl) Pyrrolidine with dimethyl formamide as solvent
Figure A20061008248102301
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles), Pyrrolidine (333 microlitres, 4.0 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 20 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and GC-MS.Obtain the GC productive rate of the calibration of 99% 5-bromo-m-xylene transformation efficiency and 74%.
Embodiment 202
In pure Pyrrolidine, prepare N-(3, the 5-3,5-dimethylphenyl) the Pyrrolidine neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and Pyrrolidine (250 microlitres, 3.0 mmoles) by syringe.This reaction mixture was stirred 20 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and GC-MS.Obtain the GC productive rate of the calibration of 86% 5-bromo-m-xylene transformation efficiency and 65%.
Embodiment 203
N-(4-chloro-phenyl-) piperidines
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), 4-bromochlorophene (191 milligrams, 1.0 mmoles) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add piperidines (148 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 20 hours at 90 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and GC-MS.Obtain the GC productive rate of the calibration of 75% 4-bromochlorophene transformation efficiency and 29%.
Embodiment 204
Prepare the 4-tertiary butyl-N-hexyl aniline by 4-tert-butyl-phenyl triflate
Figure A20061008248102312
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), and Na 2CO 3(127 milligrams, 1.2 mmoles).This test tube found time and with argon gas backfill (3 times).Add 4-tert-butyl-phenyl triflate (282 microlitres, 1.0 mmoles), normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 18 hours at 90 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC and GC-MS.Obtain the GC productive rate of 3% calibration.
Embodiment 205
The evaluation (see figure 5) of the various copper catalysts of the copper catalytic aminoization copper complex (0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing in dimethyl formamide, N, N-diethyl salicylic amide (39 milligrams, 0.2 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles), normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 24 hours at 70 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.The results are shown in Fig. 5.
Embodiment 206
The amidized evaluation of copper catalysis aryl bromide (referring to Fig. 6) in all kinds of SOLVENTS
The cuprous iodide (I) (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole)) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles), normal hexyl Amine (198 microlitres, 1.5 mmoles) and solvent (0.5 milliliter) by syringe.This reaction mixture was stirred 18 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.The results are shown in Fig. 6.
Embodiment 207
The evaluation of the various ligands of copper catalytic aminoization (referring to Fig. 7) in dimethyl formamide
In having the membranous screw cap test tube of teflon-lined, add cuprous iodide (10-19 milligram, 0.05-0.10 mmole), ligand (0.2 mmole) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add aryl bromide (1.0 mmole), normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 20 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.The results are shown in Fig. 7.
Embodiment 208
The evaluation (referring to Fig. 8) of the various ligands under the solvent-free situation in the amination of copper catalysis aryl bromide
In having the membranous screw cap test tube of teflon-lined, add cuprous iodide (10 milligrams, 0.05 mmole), ligand (0.2 mmole) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) by syringe.This gained mixture was stirred 18 hours at 100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.The results are shown in Fig. 8.
Embodiment 209
In dimethyl formamide, use the amidized evaluation of the catalytic aryl bromide of copper (referring to Fig. 9) of the catalyzer of low dosage
In having the membranous screw cap test tube of teflon-lined, add cuprous iodide (2-10 milligram, 0.01-0.05 mmole), N, N-diethyl salicylic amide (10-39 milligram, 0.05-0.20 mmole) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles), normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This gained mixture was stirred 18-54 hour at 90-100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.The results are shown in Fig. 9.
Embodiment 210
The catalytic functionalization of copper amination (referring to Figure 10)
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), aryl bromide (if solid; 1.0 mmole) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add aryl bromide (if liquid by syringe; 1.0 mmole), amine (1.5 mmole) and dimethyl formamide (0.5 milliliter).This reaction mixture was stirred 18-22 hour at 90 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by column chromatography gained resistates, provides required product.
N-hexyl-3,5-xylidine (Figure 10, clauses and subclauses 1)
Use general method, make 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (187 milligrams, 91% productive rate).
3-amino-N-hexyl aniline (Figure 10, clauses and subclauses 2)
Use general method, make 3-bromaniline (172 milligrams of microlitres, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (2: 1) wash-out, obtain the required product of colorless oil (154 milligrams, 80% productive rate).Rf=0.4 (hexane/ethyl acetate=2: 1).
4-(N-(3, the 5-3,5-dimethylphenyl) amino) butanols (Figure 10, clauses and subclauses 3)
Use general method, make 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and 4-amino butanol (138 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (2: 1) wash-out, obtain the required product of colorless oil (174 milligrams, 90% productive rate).Rf=0.4 (hexane/ethyl acetate=1: 1).
4-methyl-N-(2-(1-cyclohexenyl) ethyl) aniline (Figure 10, clauses and subclauses 4)
Use general method, make 4-bromaniline (172 milligrams, 1.0 mmoles) and 2-(1-cyclohexenyl) ethamine (209 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (205 milligrams, 95% productive rate).Rf=0.6 (hexane/ethyl acetate=10: 1).
The amino sulfo-phenylmethylether of 4-(N-benzyl) (Figure 10, clauses and subclauses 5)
Use general method, make 4-bromine sulfo-phenylmethylether (203 milligrams, 1.0 mmoles) and benzylamine (164 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (15: 1) wash-out, obtain the required product of white solid (201 milligrams, 8 8% productive rates).Rf=0.4 (hexane/ethyl acetate=10: 1).
2-(4-(N-benzyl) amino) phenoxy group) ethanol (Figure 10, clauses and subclauses 6)
Use general method, make 2-(4-bromine phenoxy group) ethanol (217 milligrams, 1.0 mmoles) and benzylamine (164 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (2: 1) wash-out, obtain the required product of colorless oil (201 milligrams, 84% productive rate).Rf=0.5 (hexane/ethyl acetate=1: 1).
3,4-(methylene radical dioxy base)-N-furfuryl group aniline (Figure 10, clauses and subclauses 7)
Use general method, make 4-bromo-1,2-(methylene radical dioxy base) benzene (120 microlitres, 1.0 mmoles) combines (132 microlitres, 1.5 mmoles) with chaff amine.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (8: 1) wash-out, obtain the required product of colorless oil (187 milligrams, 87% productive rate).Rf=0.5 (hexane/ethyl acetate=5: 1).
4-(N-hexyl) aminobenzonitrile (Figure 10, clauses and subclauses 8)
Use general method, make 4-bromobenzyl nitrile (182 milligrams, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (6: 1) wash-out, obtain the required product of faint yellow solid shape (145 milligrams, 72% productive rate).Rf=0.6 (hexane/ethyl acetate=3: 1).
4-(N-(2-methoxyl group) ethyl) aminoacetophenone (Figure 10, clauses and subclauses 9)
Use general method, make 4-bromoacetophenone (199 milligrams, 1.0 mmoles) and 2-methoxyethyl amine (130 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (1: 1) wash-out, obtain the required product of faint yellow solid shape (148 milligrams, 77% productive rate).Rf=0.6 (hexane/ethyl acetate=2: 3).
3-nitro-N-hexyl aniline (Figure 10, clauses and subclauses 10)
Use general method, make 3-bromo nitrobenzene (202 milligrams, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (6: 1) wash-out, obtain the required product of faint yellow solid shape (174 milligrams, 78% productive rate).Rf=0.5 (hexane/ethyl acetate=5: 1).
4-(N-(4-chloro-phenyl-)) amino methyl piperidines (Figure 10, clauses and subclauses 11)
Use general method, make 4-bromochlorophene (192 milligrams, 1.0 mmoles) and 4-amino methyl piperidines (171 milligrams, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use ethanol/methylene (ammonia is saturated) (1: 20) wash-out, obtain the required product of faint yellow solid shape (138 milligrams, 62% productive rate).Rf=0.3 (ethanol/methylene (ammonia is saturated) (1: 20)).
Embodiment 211
Adjacent replacement, the catalytic amination of the copper with the heterocyclic aryl bromide (referring to Figure 11) that dibromo replaces
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), aryl bromide (if solid; 1.0 mmole) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add aryl bromide (if liquid by syringe; 1.0 mmole), amine (1.2-4.0 mmole) and dimethyl formamide (0.5 milliliter).This reaction mixture was stirred 18-24 hour at 90-100 ℃.Make reaction mixture reach room temperature then.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by column chromatography gained yellow residue, provides required product.
2-methoxyl group-N-hexyl aniline (Figure 11, clauses and subclauses 1)
Use general method, 2-bromine phenylmethylether (125 microlitres, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) were reacted 22 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (30: 1) wash-out, obtain the required product of colourless liquid shape (184 milligrams, 89% productive rate).Rf=0.4 (hexane/ethyl acetate=20: 1).
2-(N-is own amino) phenylcarbinol (Figure 11, clauses and subclauses 2)
Use general method, 2-bromobenzene methyl alcohol (187 milligrams, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) were reacted 22 hours at 90 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (6: 1) wash-out, obtain the required product of colourless liquid shape (168 milligrams, 81% productive rate).Rf=0.7 (hexane/ethyl acetate=2: 1).
2-(N-2-(1-cyclohexenyl) ethyl) amino p-Xylol (Figure 11, clauses and subclauses 3)
Use general method, 2-bromine p-Xylol (138 microlitres, 1.0 mmoles) and 2-(1-cyclohexenyl) ethamine (209 microlitres, 1.5 mmoles) were reacted 24 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (30: 1) wash-out, obtain the required product of colorless oil (180 milligrams, 79% productive rate).Rf=0.5 (hexane/ethyl acetate=20: 1).
4-bromo-N-hexyl aniline (Figure 11, clauses and subclauses 4)
Use general method, make 1,4-dibromobenzene (236 milligrams, 1.0 mmoles) reacted 20 hours at 90 ℃ with normal hexyl Amine (158 microlitres, 1.2 mmoles).By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (212 milligrams, 83% productive rate).Rf=0.6 (hexane/ethyl acetate=10: 1).
N, N '-(dihexyl)-4-amino aniline (Figure 11, clauses and subclauses 5)
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (39 milligrams, 0.20 mmole), 1,4-dibromobenzene (236 milligrams, 1.0 mmoles) and K 3PO 4(636 milligrams, 3.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add normal hexyl Amine (527 microlitres, 4.0 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.This reaction mixture was stirred 42 hours at 100 ℃.Make reaction mixture reach room temperature.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.By ethyl acetate (4 * 10ml) further extractive reaction mixtures.With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by purification by silica gel column chromatography brown resistates, is used hexane/ethyl acetate (5: 1) wash-out, obtains the required product of brown solid shape (224 milligrams, 81% productive rate).Rf=0.3 (hexane/ethyl acetate=5: 1).
3-(N-(3-pyridyl) aminomethyl) piperidines (Figure 11, clauses and subclauses 6)
Use general method, 3-bromopyridine (96 microlitres, 1.0 mmoles) and 3-(aminomethyl) pyridine (153 microlitres, 1.5 mmoles) were reacted 20 hours at 90 ℃.By the silica gel column chromatography purifying crude product, use methylene dichloride (ammonia is saturated)/methyl alcohol (15: 1) wash-out, obtain the required product of weak yellow liquid shape (153 milligrams, 83% productive rate).Rf=0.4 (methylene dichloride (ammonia is saturated)/methyl alcohol=10: 1).
3-(N-(2-(1-cyclohexenyl) ethyl)) amino benzo-thiophene (Figure 11, clauses and subclauses 7)
Use general method, 3-bromine benzo-thiophene (131 microlitres, 1.0 mmoles) and 2-(1-cyclohexenyl) ethamine (209 microlitres, 1.5 mmoles) were reacted 20 hours at 90 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the liquid required product of deep yellow (211 milligrams, 82% productive rate).Rf=0.4 (hexane/ethyl acetate=20: 1).
5-(N-(4-methoxy-benzyl)) aminopyrimidine (Figure 10, clauses and subclauses 8)
Use general method, 5-bromo pyrimi piperidine (159 milligrams, 1.0 mmoles) and 4-methoxy-benzyl amine (196 microlitres, 1.5 mmoles) were reacted 22 hours at 90 ℃.By the silica gel column chromatography purifying crude product, use methylene dichloride (ammonia is saturated)/ethyl acetate (1: 1) wash-out, obtain the required product of white solid (183 milligrams, 85% productive rate).Rf=0.2 (methylene dichloride (ammonia is saturated)/ethyl acetate=1: 1)).
Embodiment 212
The amination of the aryl bromide of the catalytic functionalization of copper (referring to Figure 12) under solvent-free situation
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (10 milligrams, 0.05 mmole), and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add aryl bromide (1.0 mmole) and amine (1.5 milliliters) by syringe.This reaction mixture was stirred 18-22 hour at 90-100 ℃.Make reaction mixture reach room temperature.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by column chromatography gained resistates, provides required product.
N-hexyl-3,5-xylidine (Figure 12, clauses and subclauses 1)
Use general method, make 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) combination.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (185 milligrams, 90% productive rate).
N-(4-aminomethyl phenyl)-3,5-xylidine (Figure 12, clauses and subclauses 2)
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (10 milligrams, 0.05 mmole), 4-Tolylamine (161 milligrams, 1.5 mmoles) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) by a syringe.This reaction mixture was stirred 20 hours at 100 ℃.Make reaction mixture reach room temperature.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC, obtain the transformation efficiency of 22% 5-bromo-m-xylene and the GC productive rate of 9% required product.
N-(3, the 5-3,5-dimethylphenyl) indoles (Figure 12, clauses and subclauses 3)
The neutralized verdigris (10 milligrams, 0.05 mmole) of in the test tube that teflon-lined barrier film screw cap is housed, packing into, N, N-diethyl salicylic amide (10 milligrams, 0.05 mmole), indoles (176 milligrams, 1.5 mmoles) and K 3PO 4(425 milligrams, 2.0 mmoles).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles) by a syringe.This reaction mixture was stirred 20 hours at 100 ℃.Make reaction mixture reach room temperature.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC or GC-MS.By the further extractive reaction mixture of ethyl acetate (4 * 10 milliliters).With the organic phase salt water washing that merges, use dried over sodium sulfate.Solvent removed in vacuo by the purification by silica gel column chromatography yellow residue, is used hexane/ethyl acetate (10: 1) wash-out, obtains the required product of brown solid shape (196 milligrams, 89% productive rate).
3-nitro-N-hexyl aniline (Figure 12, clauses and subclauses 4)
Use general method, 3-bromo nitrobenzene (202 milligrams, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) were reacted 22 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (6: 1) wash-out, obtain the required product of faint yellow solid shape (132 milligrams, 59% productive rate).Rf=0.5 (hexane/ethyl acetate=5: 1).
3-amino-N-hexyl aniline (Figure 15, clauses and subclauses 5)
Use general method, 3-bromaniline (172 milligrams, 1.0 mmoles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) were reacted 20 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (2: 1) wash-out, obtain the required product of colorless oil (137 milligrams, 71% productive rate).Rf=0.4 (hexane/ethyl acetate=2: 1).
4-methyl-N-(2-(1-cyclohexenyl) ethyl) aniline (Figure 12, clauses and subclauses 6)
Use general method, 4-toluene bromide (172 milligrams, 1.0 mmoles) and 2-(1-cyclohexenyl) ethamine (209 microlitres, 1.5 mmoles) were reacted 20 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (20: 1) wash-out, obtain the required product of colorless oil (198 milligrams, 92% productive rate).Rf=0.6 (hexane/ethyl acetate=10: 1).
4-(N-(4-chloro-phenyl-)) amino methyl piperidines (Figure 12, clauses and subclauses 7)
Use general method, 4-bromochlorophene (192 milligrams, 1.0 mmoles) and 4-amino methyl piperidines (171 milligrams, 1.5 mmoles) were reacted 20 hours at 100 ℃.By the silica gel column chromatography purifying crude product, use ethanol/methylene (ammonia is saturated) (1: 20) wash-out, obtain the required product of faint yellow solid shape (134 milligrams, 60% productive rate).Rf=0.3 (ethanol/methylene (ammonia is saturated)=1: 20).
3-(N-hexyl) aminopyridine (Figure 12, clauses and subclauses 8)
Use general method, 3-bromopyridine (96 microlitres, 1.0 Bo moles) and normal hexyl Amine (198 microlitres, 1.5 mmoles) were reacted 18 hours at 90 ℃.By the silica gel column chromatography purifying crude product, use hexane/ethyl acetate (1: 1) wash-out, obtain the required product of colorless oil (146 milligrams, 82% productive rate).Rf=0.2 (hexane/ethyl acetate=2: 1).
Embodiment 213
The C-arylation of triethyl phosphine acyl acetic acid ester
Use the method for phenyl-iodide
Heating the time finds time to be equipped with the Schlenk test tube of the oven dry of magnetic stirring bar and tetrafluoroethylene stopcock, and cools off under argon atmospher.Cuprous iodide (9.8 milligrams, 5.1 moles of %) and CS pack in the test tube 2CO 3(0.434 gram, 1.33 mmoles).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.By volume add Trans-1,2-diamino-cyclohexane (12 microlitres, 10.0 moles of %) then adds phenyl-iodide (114 microlitres, 1.00 mmoles), triethyl phosphine acyl acetic acid ester (220 microlitres, 1.11 mmoles), and dry toluene (1.0 milliliters).Under the argon gas positive pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and with sealed tube preheating in 70 ℃ of oil baths.After 22 hour time, make the reactant cool to room temperature, and between ethyl acetate (20 milliliters) and saturated aqueous ammonium chloride (10 milliliters), distribute.With organic moiety drying (sodium sulfate) and pass through diatomite filtration.By gas chromatographic analysis solution, the GC productive rate that the demonstration phenyl-iodide is converted into above-claimed cpd is 93%.
Use the method for bromobenzene
Heating the time finds time to be equipped with the Schlenk test tube of the oven dry of magnetic stirring bar and tetrafluoroethylene stopcock, and cools off under argon atmospher.Cuprous iodide (9.5 milligrams, 5.0 moles of %) and CS pack in the test tube 2CO 3(0.428 gram, 1.31 mmoles).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.By volume add Trans-1,2-diamino-cyclohexane (12 microlitres, 10.0 moles of %) then adds bromobenzene (109 microlitres, 1.00 mmoles), triethyl phosphine acyl acetic acid ester (220 microlitres, 1.11 mmoles), and dry toluene (1.0 milliliters).Under the argon gas positive pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and with sealed tube preheating in 70 ℃ of oil baths.16.5 after hour time, make the reactant cool to room temperature, and between ethyl acetate (20 milliliters) and saturated aqueous ammonium chloride (10 milliliters), distribute.With organic moiety drying (sodium sulfate) and pass through diatomite filtration.By gas chromatographic analysis solution, the GC productive rate that the demonstration bromobenzene is converted into above-claimed cpd is 2%.
Embodiment 214
The C-arylation of deoxybenzoin
Figure A20061008248102411
Heating the time finds time to be equipped with the Schlenk test tube of the oven dry of magnetic stirring bar and tetrafluoroethylene stopcock, and cools off under argon atmospher.In test tube, pack into cuprous iodide (9.4 milligrams, 4.9mol%), K 3PO 4(0.435 gram, 2.05 mmoles), 4-iodoanisole (0.235 gram, 1.00 mmoles), and deoxybenzoin (0.295 gram, 1.46 mmoles).This test tube found time and with argon gas filling (3 times), and replace rubber septum with the tetrafluoroethylene stopcock.By volume add Trans-1, (1 2 microlitres 10.0mol%), then add dry toluene (1.0 milliliters) to the 2-diamino-cyclohexane.Under Ar Pressure, use the tetrafluoroethylene stopcock to substitute barrier film, and sealed tube is placed in the oil bath of 110 ℃ of preheatings.After 42 hour time, make the reactant cool to room temperature, and between ethyl acetate (20 milliliters) and saturated aqueous ammonium chloride (10 milliliters), distribute.With organic moiety drying (sodium sulfate), use diatomite filtration, and concentrate with rotary evaporation.Oil by therefore the silica gel chromatography purifying obtains obtains light yellow oily product (64 milligrams, 21%).
Embodiment 215
Use N, N '-dimethyl-ethylenediamine prepares benzonitrile as ligand by phenyl-iodide and cupric cyanide
The cupric cyanide (108 milligrams, 1.21 mmoles) of packing in the Schlenk test tube is found time the filling argon gas.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (21.5 microlitres, 0.202 mmole, 20mol%), phenyl-iodide (112 microlitres, 1.00 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 17 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows required product by GC is 31%.
Embodiment 216
Use N, N '-dimethyl-ethylenediamine prepares 3, the 5-xylylic acid nitrile as ligand by 5-bromo-m-xylene and potassium cyanide
In a Schlenk pipe, pack into cuprous iodide (19.5 milligrams, 0.102 mmole, 20mol%), KCN (78 milligrams, 1.20 mmoles) finds time and the filling argon.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (21.5 microlitres, 0.202 mmole, 20mol%), five-bromo-m-xylene (136 microlitres, 1.00 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Add dodecane (mark in 230 microlitres, GC), ethyl acetate (2 milliliters) and 30% ammoniacal liquor (1 milliliter).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows required product by GC is 15%.
Embodiment 217
The catalytic indoles arylation of copper in dioxane (Figure 13) with 4-toluene bromide and various ligands
In the flame-dried test tube that can seal again, add cuprous iodide (1mol%), indoles (1.2 mmole) and K 3PO 4(2.1 mmole).Test tube is fixed with rubber septum, find time and the backfill argon gas, hexene is this repeatedly finds time/the backfill step.Under argon atmospher, in this test tube, add 4-toluene bromide (1.0 mmole) successively, ligand (10mol%), dodecane (mark in 0.20 mmole, GC) and dioxane (1 milliliter).Reaction tube used nut sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Analyze filtrate by GC, and compare, obtain gauged GC productive rate (Figure 13) with the known sample of confirming product.
Embodiment 218
The catalytic indoles arylation of copper in toluene (Figure 14) with 4-toluene bromide and various ligands
Implement the method that embodiment 217 describes with toluene (1 milliliter) as solvent.The ligand of using is described in Figure 14.Gauged GC productive rate is shown in Figure 14.
Embodiment 219
The catalytic indoles arylation of copper in toluene (Figure 15 and 16) with 2 bromo toluene and various ligands
In the flame-dried test tube that can seal again, add cuprous iodide (1mol%), indoles (1.0 mmole) and K 3PO 4(2.1 mmole).Test tube is fixed with rubber septum, find time and the backfill argon gas, hexene is this repeatedly finds time/the backfill step.Under argon atmospher, in this test tube, add 2 bromo toluene (1.0 mmole) successively, ligand (20mol%, Figure 15 or 16), dodecane (mark in 0.20 mmole, GC) and toluene (1 milliliter).Reaction tube used nut sealing and with inclusion heated and stirred 24 hours in 110 ℃ oil bath.Reaction mixture is cooled to envrionment temperature, with the dilution of 2-3 milliliter ethyl acetate, and by the silica gel plug filtration, with 10-20 milliliter eluent ethyl acetate.Analyze filtrate by GC, and compare, obtain gauged GC productive rate (being shown in Figure 15 and 16) with the known sample of confirming product.
Embodiment 220
By N, the arylation of the ethanamide that O-two (trimethyl silyl) ethanamide produces on the spot
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), KF (350 milligrams, 6.0 mmoles) finds time and the filling argon.Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), 2-toluene iodide (128 microlitres, 1.01 mmoles), N, O-two (trimethyl silyl) ethanamide (300 microlitres, 1.21 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 16 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.With gained suspension cool to room temperature, filter by 0.5 * 1 centimetre of silicagel pad then, with ethyl acetate (20 milliliters) wash-out.Concentrated filtrate dodges (2 * 15 centimetres of formula purification by chromatography resistatess with silica gel; Hexane-ethyl acetate 1: 4; 15 milliliters of flow points).Flow point 10-17 obtains 78 milligrams (52% productive rate) white needle shape N-(2-aminomethyl phenyl) ethanamide.
Embodiment 221
Use cupric acetylacetonate (II) or 2,2,6,6-tetramethyl--3,5-pimelic acid copper (II) is as the arylation of the N-phenylacetamide of catalyzer
The cupric acetylacetonate (II) (14 milligrams, 0.054 mmole, 5.1 moles of %) of in the Schlenk test tube, packing into, N-phenylacetamide (165 milligrams, 1.22 mmoles), Cs 2CO 3(460 milligrams, 1.41 mmoles) find time to use the argon gas filling.The stock solution that in an independent flask, prepares 5-iodine m-xylene (3.0 milliliters) in the dioxane (20 milliliters) and dodecane (mark in the GC, 4.7 milliliters).The stock solution (1.4 milliliters) that a part is contained the 5-iodine m-xylene of 1.05 mmoles under argon atmospher adds the Schlenk test tube.Schlenk was stirred 22 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained white suspension reach room temperature.The sample of 0.1 milliliter of this suspension is filtered by plug of celite, with ethyl acetate (1 milliliter) wash-out.Analyze filtrate by GC, the productive rate of required product is 58%.
Use 2,2,6,6-tetramethyl--3,5-pimelic acid copper (II) (23 milligrams, 0.054 mmole 5.1mol%) replaces cupric acetylacetonate (II), 110 ℃ of reactions 24 hours, it was 68% that GC analyzes the productive rate that shows N-(3, the 5-3,5-dimethylphenyl)-N-phenylacetamide.
Embodiment 222
Use the arylation (Figure 17) of the N-phenylacetamide of various ligands
The cuprous iodide (10 milligrams, 0.053 mmole, 5.0 moles of %) of in the Schlenk test tube, packing into, ligand (when ligand is solid) N-phenylacetamide (165 milligrams, 1.22 mmoles), Cs 2CO 3(460 milligrams, 1.41 mmoles) find time to use the argon gas filling.Under argon atmospher, add ligand (when ligand is liquid), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), dodecane (mark in the GC, 235 microlitres), and dioxane (1.0 milliliters).The Schlenk test tube was stirred 23 hours at 110 ℃ of magnetic with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Make gained suspension reach room temperature.The sample of 0.1 milliliter of this suspension is filtered by plug of celite, use ethyl acetate (1 milliliter) wash-out, and analyze this filtrate by GC.The results are shown in Figure 17.
Embodiment 223
Use variously 1,2-diamines ligand makes 2-Pyrrolidone arylation (Figure 18) by 5-iodine m-xylene
In the Schlenk pipe, pack into cuprous iodide (10 milligrams, 0.052 mmole, 5.0mol%), K 3PO 4(450 milligrams, 2.1 mmoles) find time and the filling argon.Under argon atmospher, add ligand (0.11 mmole, 10mol%), 5-iodine m-xylene (150 microlitres, 1.04 mmoles), 2-Pyrrolidone (94 microlitres, 1.24 mmoles) and dioxane (1.0 milliliters).The Schlenk test tube was stirred 4 hours at 60 ℃ of magnetic with tetrafluoroethylene jam pot cover mouth and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in the GC, 235 microlitres) and ethyl acetate (1 milliliter).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyze this sample by GC.The results are shown in Figure 18.
Embodiment 224
Use variously 1,2-diamines ligand makes N-benzyl methane amide arylation (Figure 19) by the 5-bromo-m-xylene
10 * 3 millimeters stirring rod that scribble polytetrafluorethylecoatings coatings of in ten the 15 milliliters test tube with screw thread, packing into, add cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%) and K 2CO 3(280 milligrams, 2.03 mmoles).Each test tube is found time by 21 gage needles, then the filling argon gas with the no top nut sealing that the teflon-lined silicone rubber membrane is housed.Simultaneously, under argon gas atmosphere, in 25 milliliters of pyriform flasks, prepare 5-bromo-m-xylene (2.04 milliliters, 15.0 mmoles) N-benzyl methane amide (2.44 grams, 18.1 mmoles), and the stock solution of dodecane (mark in the GC, 0.68 milliliter) in toluene (15 milliliters).Use syringe to add 1.28 milliliters of stock solutions, then add ligand to each test tube.Reaction mixture in the test tube was stirred 22 hours in 110 ± 5 ℃ oil bath.Make test tube reach room temperature then, remove screw cap, add ethyl acetate (2 milliliters).The supernatant liquid sample of each test tube of 50-100 microlitre is diluted with ethyl acetate (1 milliliter), analyze gained solution by GC.The results are shown in Figure 19.
Embodiment 225
Use the N-methylformamide arylation (Figure 20) of various ligands
10 * 3 millimeters stirring rod that scribble polytetrafluorethylecoatings coatings of in six the 15 milliliters test tube with screw thread, packing into, add cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), ligand is (when this ligand is solid; 0.10 mmole), and K 2CO 3(430 milligrams, 2.03 mmoles).Each test tube is found time by 21 gage needles, then the filling argon gas with the no top nut sealing that the teflon-lined silicone rubber membrane is housed.Simultaneously, under argon gas atmosphere, in 25 milliliters of pyriform flasks, prepare 5-iodine m-xylene (2.16 milliliters, 15.0 mmoles) N-methylformamide (1.06 milliliters, 18.1 mmoles), and the stock solution of dodecane (mark in the GC, 0.68 milliliter) in toluene (15 milliliters).Use syringe to add 1.28 milliliters of stock solutions that contain 1.0 mmole 5-iodine m-xylenes and 1.2 mmole N-methylformamide, then add ligand (when this ligand is liquid 0.10 to each test tube; Mmole).Cover this barrier film top with vacuum grease then, so that the closed injection spot.Reaction mixture in the test tube was stirred 24 hours in 110 ± 5 ℃ oil bath.Make test tube reach room temperature then, remove screw cap, add ethyl acetate (3 milliliters).The supernatant liquid sample of each test tube of 50-100 microlitre is diluted with ethyl acetate (1 milliliter), analyze gained solution by GC.The results are shown in Figure 20.
Embodiment 226
Use the arylation of di-t-butyl phosphine oxide as the N-methylformamide of ligand
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), di-t-butyl phosphine oxide (16.5 milligrams, 0.102 mmole), K 3PO 4(430 milligrams, 2.03 mmoles) find time and the filling argon.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), N-methylformamide (72 microlitres, 1.23 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows required product by GC is 46%.
Embodiment 227
Use the arylation of hexamethylphosphorictriamide as the N-methylformamide of ligand
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), K 3PO 4N (430 milligrams, 2.03 mmoles) finds time and the filling argon.Under argon atmospher, add hexamethylphosphorictriamide (18.5 microlitres, 0.102 mmole, 10mol%), 5-iodine m-xylene (145 microlitres, 1.00 mmoles), N-methylformamide (72 microlitres, 1.23 mmoles), and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows N-(3, the 5-3,5-dimethylphenyl)-N-methylformamide by GC is 76%.
Embodiment 228
Use 3,1 '-dimethyl-4,5-dihydro-3H, 1 ' H-[1,2 '] arylation of the N-methylformamide of diimidazole base-2-ketone conduct
In the Schlenk test tube, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%) 3,1 '-dimethyl-4,5-dihydro-3H, 1 ' H-[1,2 '] diimidazole base-2-ketone (and 18 milligrams, 0.10 mmole, 10mol%), K 3PO 4(430 milligrams, 2.03 mmoles) find time, and use the argon filling.Under argon atmospher, add 5-iodine m-xylene (145 microlitres, 1.00 mmoles), N-methylformamide (72 microlitres, 1.23 mmoles) and toluene (1.0 milliliters).The Schlenk test tube was stirred 24 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows N-(3, the 5-3,5-dimethylphenyl)-N-methylformamide by GC is 54%.
Embodiment 229
Use the N-methylformamide arylation (Figure 21) in various copper source
10 * 3 millimeters stirring rod that scribble tetrafluoroethylene and the K that packs into respectively pack in nine the 15 milliliters test tube with screw thread 3PO 4In (430 milligrams, 2.03 mmoles) and the following copper source one: 1) copper powder, bronze (Aldrich, 99%; 3.2 milligram, 0.050 mmole); 2) cuprous iodide (Strem, 98%; 9.6 milligram, 0.050 mmole); 3) cuprous chloride (Strem, 97+%; 5.0 milligram, 0.050 mmole); 4) CuSCN (Aldrich, 98+%; 6.1 milligram, 0.050 mmole); 5) cupric oxide (AlfaAesar, 99%; 3.6 milligram, 0.025 mmole); 6) cupric chloride (Strem, 98%; 6.8 milligram, 0.051 mmole); 7) CuSO4.5H2O (AIdrich, 98+%; 12.5 milligram, 0.0501 mmole); 8) venus crystals (Strem, 99%; 9.1 milligram, 0.050 mmole); 9) cupric acetylacetonate (II) (Lancaster, 98%; 13.1 milligram, 0.0500 mmole).Each test tube is found time by 21 gage needles, then the filling argon gas with the no top nut sealing that the teflon-lined silicone rubber membrane is housed.Simultaneously, under argon gas atmosphere, in 25 milliliters of pyriform flasks, prepare (2.16 milliliters of 5-iodine m-xylenes, 15.0 mmole) the N-methylformamide is (1.06 milliliters, 18.1 mmole), N, N '-dimethyl-ethylenediamine (160 microlitres, 1.50 mmoles) and dodecane (mark in the GC, the 0.68 milliliter) stock solution in toluene (15 milliliters).Use syringe in each test tube, to add 1.28 milliliters and contain 1.0 mmole 5-iodine m-xylenes, 1.2 mmole N-methylformamide, 0.10 mmole N, the stock solution of N '-dimethyl-ethylenediamine.Cover this barrier film top with vacuum grease then, so that the closed injection spot.Reaction mixture in the test tube was stirred 7 hours in 80 ± 5 ℃ oil bath.Make test tube reach room temperature then, remove screw cap, add ethyl acetate (2 milliliters).The supernatant liquid sample of each test tube of 50-100 microlitre is diluted with ethyl acetate (1 milliliter), analyze gained solution by GC.The results are shown in Figure 21.
Embodiment 230
Use the arylation (Figure 22) of the N-methyl-4-methyl benzenesulfonamide of various alkali
The cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0 moles of %) of packing in the Schlenk test tube, alkali (2.0-4.1 mmole) is found time, filling argon (work as N, N, N ', N '-tetramethyl guanidine be during as alkali, with behind the argon filling Schlenk test tube with its adding).Under argon atmospher, add N, and N '-dimethyl-ethylenediamine (11 microlitres, 0.10 mmole, 10mol%), phenyl-iodide (112 microlitres, 1.00 mmoles) and toluene (1.0 milliliters).Schlenk was stirred 22 hours at 110 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make gained suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC) and ethyl acetate (3 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyze this sample by GC.The results are shown in Figure 22.
Embodiment 231
Use the arylation of tri-potassium phosphate as the 2-Pyrrolidone of alkali
10 * 3 millimeters stirring rod that scribble polytetrafluorethylecoatings coatings of in having the test tube of screw thread, packing into, add cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%) and K 5P 3O 10(Strem, fine grinding, 430 milligrams, 0.96 mmole).Developmental tube is found time by 21 gage needles, then the filling argon gas with the no top nut sealing that the teflon-lined silicone rubber membrane is housed.Simultaneously, under argon atmospher, in 25 milliliters of pyriform flasks, prepare 5-iodine m-xylene (2.16 milliliters), 2-Pyrrolidone (1.40 milliliters), and the stock solution of dodecane (mark in the GC, 0.68 milliliter) in toluene (15 milliliters).Syringe adds the stock solution (1.28ml) that a part contains 1.0 mmole 5-iodine m-xylenes and 1.2 mmole 2-Pyrrolidones, then add the N-methyl ethylenediamine (8.9 microlitres, 1.0 mmoles, 10mol%).Reaction mixture in the test tube was stirred 5 hours in 60 ± 5 ℃ oil bath.Make test tube reach room temperature then, remove nut, add ethyl acetate (2 milliliters).Dilute the 50-100 microlitre sample solution of this test tube supernatant liquid with ethyl acetate (1 milliliter).It is 95% that the GC of gained solution analyzes the productive rate that shows N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone.
Use N, (11 microlitres, 1.0 mmoles 10mol%) replace the N-methyl ethylenediamine to N '-dimethyl-ethylenediamine, and it is 93% that GC analyzes the productive rate that shows N-(3,5 3,5-dimethylphenyl)-2-Pyrrolidone.
(6.8 microlitres, 1.0 mmoles 10mol%) replace the N-methyl ethylenediamine, and it is 61% that GC analyzes the productive rate that shows N-(3, the 5-3,5-dimethylphenyl)-2-Pyrrolidone to use quadrol.
Embodiment 232
Use the arylation (Figure 23) of the normal hexyl Amine of various alkali
In being housed, the membranous screw cap test tube of teflon-lined adds cuprous iodide (10 milligrams, 0.05 mmole), alkali (2.0 mmole) and N, N-diethyl salicylic amide (39 milligrams, 0.2 mmole).This test tube found time and with argon gas backfill (3 times).Add 5-bromo-m-xylene (136 microlitres, 1.0 mmoles), normal hexyl Amine (198 microlitres, 1.5 mmoles) and dimethyl formamide (0.5 milliliter) by syringe.Reaction mixture is stirred and heated 18 hours at 90 ℃.Make test tube reach room temperature.Add ethyl acetate (～2 milliliters), water (～10 milliliters), ammonium hydroxide (～0.5 milliliter) and dodecane (227 microlitre).Analyze organic phase by GC.The results are shown in Figure 23.
Embodiment 233
Use the arylation (Figure 24) of the benzylamine of various alkali
In the membranous screw cap test tube of teflon-lined is housed, pack into cuprous iodide (19 milligram of 0.1 mmole) and alkali (2.0 mmole).Test tube found time and with argon gas backfill (3 times).Add Virahol (1.0 milliliters), ethylene glycol (111 microlitres, 2.0 mmoles), phenyl-iodide (112 microlitres, 1.0 mmoles) and benzylamine (131 microlitres, 1.2 mmoles) by micro-syringe.Reaction mixture is stirred and heated 18 hours at 80 ℃.Make reaction mixture reach room temperature.Add ether (～2 milliliters), water (～10 milliliters) and dodecane (227 microlitre).Analyze organic phase by GC.The results are shown in Figure 24.
Embodiment 234
Use the arylation (Figure 25) of various glycol as the benzylamine of ligand
In the membranous screw cap test tube of teflon-lined is housed, pack into cuprous iodide (19 milligrams, 0.1 mmole) and anhydrous K 3PO 4(425 milligrams, 2.0 mmoles).Test tube found time and with argon gas backfill (3 times).Add Virahol (1.0 milliliters, not necessarily), ethylene glycol (0.1-2.0 mmole), phenyl-iodide (112 microlitres, 1.0 mmoles) and benzylamine (131 microlitres, 1.2 mmoles) by syringe if glycol is used as solvent.Reaction mixture is stirred and heated 18 hours at 80 ℃.Make reaction mixture reach room temperature.Add ether (～2 milliliters), water (～10 milliliters) and dodecane (227 microlitre).Analyze organic phase by GC.The results are shown in Figure 25.
Embodiment 235
The benzylamine arylation that causes on the spot by N-benzyl-trifluoroacetamide
In the Schlenk pipe, pack into cuprous iodide (9.6 milligrams, 0.050 mmole, 5.0mol%), N-benzyl trifluoroacetamide (244 milligrams, 1.20 mmoles), K 3PO 4(640 milligrams, 3.01 mmoles) find time and the filling argon.Under argon atmospher, add phenyl-iodide (112 microlitres, 1.00 mmoles), ethylene glycol (0.11 milliliter, 2.0 mmoles) and Virahol (1.5 milliliters).The Schlenk test tube was stirred 24 hours at 80 ℃ with tetrafluoroethylene valve channel closure and with reaction mixture.Make the gained white suspension reach room temperature.Add dodecane (mark in 230 microlitres, GC), ethyl acetate (2 milliliters) and 30% ammoniacal liquor (2 milliliters).Dilute 0.1 ml sample of this supernatant liquid with ethyl acetate (1 milliliter), analyzing the productive rate that shows N-phenylbenzyl amine by GC is 76%.
Embodiment 236
Use the arylation (Figure 26) of the normal hexyl Amine of various ligands
It is tight that eight screw thread test tubes are sent into the glove box and the lid that fill nitrogen, removes from glove box then.In air with cuprous iodide (9.5 milligrams, 0.050 mmole, 5.0mol%), ligand (when ligand is solid) and K 3PO 4(440 milligrams, 2.07 mmoles) add test tube.Test tube is lid immediately, sends into the glove box that fills nitrogen, removes lid before finding time immediately.In glove box inside, test tube is covered by the screw cap that is lined with silicone rubber membrane that does not have the top, removes from glove box then.In independent flask, preparation bromobenzene (1.05 milliliters) and the stock solution of normal hexyl Amine (1.60 milliliters) in propyl carbinol (10 milliliters).Use syringe to add ligand (when ligand during) and a part of stock solution (1.3 milliliters) that contains 1.0 mmole bromobenzenes and 1.2 mmole normal hexyl Amines as liquid.Test solid screw cap replaces not having the screw cap on top.This reaction mixture 100 ℃ of heating 23 hours, is allowed to reach room temperature then.Add dodecane (mark in 230 microlitres, GC), ethyl acetate (2 milliliters), and water (1 milliliter).Dilute 0.1 milliliter sample of this supernatant liquid with ethyl acetate (1 milliliter), analyze this sample by GC.The results are shown in Figure 26.
With reference to compilation
All patents and publication that this specification sheets is quoted enroll hereby as a reference.
Equivalent
As well known to those skilled in the artly maybe can use routine test to determine, the technical scheme that is equal to the disclosed concrete scheme of the present invention of the application.Such equivalent is included in the following claim.

Claims (273)

1. the method for a flow process 2 expressions:
Wherein
X represents I, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly;
(N-heteroaryl)-H represents the pyrazoles that replaces, pyrroles, tetrazolium, imidazoles non-imposedly; indazole, 1,2,3-triazoles; 1,2,4-triazole, indole carbazole; benzotriazole, benzoglyoxaline, guanine, purine; VITAMIN B4, xanthine, 8-azaadenine, 8-azo A Piao xanthine; uridylic, 6-azauracil, cytosine(Cyt), thymus pyrimidine; the 6-azathymine, uric acid, benzoylene urea, 4 (3H)-pyrimidones; pyridone, 1 (2H)-2 ketone, 1; 2,3-phentriazine-4 (3H)-ketone, 2-benzoxazol quinoline ketone, thymidine; uridine, (-)-inosine 1H-1,2,3,5-diazadiphosphole, 1H-1,2,3-azadiphosphole, 1H-1,2,4-azadiphosphole, 1H-1,2,4-diazaphosphole, 1H-1,2,3-diazaphosphole, 1H-1,3,2-diazaphosphole, 1H-1,2-azadiphosphole, 1H-1,3-azadiphosphole, 1H-1,2,3,4-triazaphosphole, 1H-1,2,3,5-dithiadiazolidene, 1H-1,3,2,4-dithiadiazolidene, 1,3,2-oxa-thiazole, 3H-1,3,2-oxa-thiazole, 1,3, the 2-dithiazole, 1H-1,2-azaborole, pentazole, 3H-1,2,3-two  azoles, 2H-1,2,3-oxa-diazine, 2H-1,2,4-oxa-diazine, 2H-1,2,5-oxa-diazine, 2H-1,2,6-oxa-diazine, 2H-1,2,3-thiadiazine, 2H-1,2,4-thiadiazine, 2H-1,2,5-thiadiazine, 2H-1,2,6-thiadiazine, 2H-1,2-thiazine, 1,3,5,2,4,6-three thia triazines, 2H-1,2,4,5-oxa-triazine, 4H-1,3,2,4-dithia diazine, 2H, 4H-1,3,2,5-two oxa-diazines, 2H-1,5,2,4-two oxa-diazines, 2H-1,2,4,6-thia triazine, 2H-1,2,4,5-thia triazine, 4H-1,3,2-dithiazine alkane, 4H-1,3,2-two  piperazines, 2H-1,5,2-two  piperazines, 1,3,4-dithiazine alkane, 4H-1,3, the 2-oxa-thiazine, 2H, 4H-1,5,2-oxa-thiazine, 2H-1,2-diaza , 2H-1,3-diaza , 2H-1,4-diaza , 2H-1,2,5-three azepine , 2H-1,3,5-three azepine , 2H-1,2,4-three azepine  1H-azepine , 2H-1,2,3,5-four azepine , 2H-1,2,4,6-four azepine , 2H-1,2,4,5-four azepine , 2H-1,5,2,4-dithia diaza , 1,3,5,2,4,7-three thias three azepine , 1,3,5,2,4-three thia diaza , pentahydro--1,3,5,2,4,6,8-three thias four bifurcations are hot because of, 2H, 6H-1,5,2,4,6,8-dithia four bifurcations hot because of, 2H-1,2,5-oxa-two bifurcations hot because of, 2H-1,2,6-oxa-two bifurcations are hot because of, 2H-1, and 2-oxa-bifurcation is hot because of, 2H-1,2-thia bifurcation hot because of, 4H-1,2,5-thia two bifurcations hot because of, 2H-1,2, assorted two bifurcations of 6-thia hot because of, 5H-[1,2,4]-thiadiazoles [1,5-b] [1 also, 2,4] oxa-thiazole, triazolothiadiazole, thienothiadiazole 1H-imidazo [1,2-a] imidazoles, 4H-furans [3,2-b] pyrroles [3,4-b], 1H-pyrrolo-pyrazoles, 1H-[2,3-d] the thieno-pyrazoles, 1H-[2,4-d] the thieno-pyrazoles, 1H-[2,3-c] the thieno-pyrazoles, 1H-[3,4-c] the thieno-pyrazoles, 1H-1,3-benzazaphole, 1The H-benzazepine, the 2H-2-benzazepine, 1H-1, the 3-benzodiazepine, 1H-1, the 4-benzodiazepine, 1H-1, the 5-benzodiazepine, 1H-1,2,4-benzo three azepine , 1H-1,2,5-benzo three azepine , 1H-1,3,4-benzo three azepine , or 3H-3-benzazepine;
Catalyzer comprises copper atom or ion, and ligand; And
Alkali is represented brnsted base.
2. the process of claim 1 wherein that X represents iodine.
3. the process of claim 1 wherein that X represents bromine.
4. the process of claim 1 wherein that X represents chlorine.
5. the process of claim 1 wherein that the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
6. the process of claim 1 wherein that the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, the 2-diamino-cyclohexane, or 1,2-diamino alkane.
7. the process of claim 1 wherein that the ligand that catalyzer comprises is selected from 2-phenylphenol, 2, the 2-isopropyl-phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
8. the process of claim 1 wherein that the ligand that catalyzer comprises is a chelating ligand.
9. the process of claim 1 wherein ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
10. claim 1 method, wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1.
11. the process of claim 1 wherein that the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
12. the method for claim 1,, wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
13. the process of claim 1 wherein that alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
14. the process of claim 1 wherein that catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
15. the process of claim 1 wherein that catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
16. the process of claim 1 wherein that catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
17. the process of claim 1 wherein that catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
18. the process of claim 1 wherein that temperature that this method carries out is less than about 150 ℃.
19. the process of claim 1 wherein that temperature that this method carries out is less than about 140 ℃.
20. the process of claim 1 wherein that temperature that this method carries out is less than about 110 ℃.
21. the process of claim 1 wherein that temperature that this method carries out is less than about 100 ℃.
22. the process of claim 1 wherein that temperature that this method carries out is less than about 90 ℃.
23. the process of claim 1 wherein that temperature that this method carries out is less than about 50 ℃.
24. the process of claim 1 wherein that temperature that this method carries out is less than about 40 ℃.
25. the process of claim 1 wherein that this method carries out at ambient temperature.
26. the process of claim 1 wherein that Z represents the aryl that replaces non-imposedly.
27. the process of claim 1 wherein that Z represents the phenyl that replaces non-imposedly.
28. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
29. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
30. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
31. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
32. the process of claim 1 wherein that X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
33. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
34. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
35. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
36. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
37. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
38. the process of claim 1 wherein that X represents I; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
39. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
40. the process of claim 1 wherein that X represents I; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
41. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
42. the process of claim 1 wherein that X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
43. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
44. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
45. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
46. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
47. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
48. the process of claim 1 wherein that X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
49. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
50. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
51. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
52. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
53. the process of claim 1 wherein that X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
54. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
55. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
56. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
57. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
58. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
59. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
60. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
61. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
62. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
63. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
64. the process of claim 1 wherein that X represents bromine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
65. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
66. the process of claim 1 wherein that X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
67. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
68. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
69. the process of claim 1 wherein that X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
70. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
71. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
72. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
73. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
74. the process of claim 1 wherein that X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
75. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
76. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
77. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
78. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
79. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
80. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
81. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
82. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
83. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
84. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
85. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
86. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
87. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
88. the process of claim 1 wherein that X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
89. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N ,-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
90. the process of claim 1 wherein that X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
91. the method for flow process 3 expressions:
Flow process 3
Wherein
X represents I, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly;
Catalyzer comprises copper atom or ion, and ligand; And
Alkali is represented brnsted base; And
R represents the alkyl that replaces, cycloalkyl, aralkyl, heteroaralkyl, alkenyl alkyl, or alkynyl alkyl non-imposedly.
92. the method for claim 91, wherein X represents iodine.
93. the method for claim 91, wherein X represents bromine.
94. the method for claim 91, wherein X represents chlorine.
95. the method for claim 91, wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
96. the method for claim 91, wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
97. the method for claim 91, wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 2-isopropyl-phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
98. the method for claim 91, wherein the ligand that comprises of catalyzer is a chelating ligand.
99. the method for claim 91, wherein the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
100. claim 91 method, wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1.
101. the method for claim 91, wherein the ligand that comprises of catalyzer is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
102. the method for claim 91,, wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
103. the method for claim 91, wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
104. the method for claim 91, wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
105. the method for claim 91, wherein catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
106. the method for claim 91, wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
107. the method for claim 91, wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
108. the method for claim 91, wherein this method temperature of carrying out is less than about 150 ℃.
109. the method for claim 91, wherein this method temperature of carrying out is less than about 140 ℃.
110. the method for claim 91, wherein this method temperature of carrying out is less than about 110 ℃.
111. the method for claim 91, wherein this method temperature of carrying out is less than about 100 ℃.
112. the method for claim 91, wherein this method temperature of carrying out is less than about 90 ℃.
113. the method for claim 91, wherein this method temperature of carrying out is less than about 50 ℃.
114. the method for claim 91, wherein this method temperature of carrying out is less than about 40 ℃.
115. the method for claim 91, wherein this method is carried out at ambient temperature.
116. the method for claim 91, wherein Z represents the aryl that replaces non-imposedly.
117. the method for claim 91, wherein Z represents the phenyl that replaces non-imposedly.
118. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
119. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
120. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
121. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
122. the method for claim 91, wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
123. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
124. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
125. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
126. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
127. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
128. the method for claim 91, wherein X represents I; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
129. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
130. the method for claim 91, wherein X represents I; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
131. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
132. the method for claim 91, wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
133. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
134. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
135. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
136. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
137. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
138. the method for claim 91, wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
139. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
140. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
141. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
142. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
143. the method for claim 91, wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
144. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
145. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
146. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
147. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
148. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
149. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
150. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
151. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
152. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
153. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
154. the method for claim 91, wherein X represents bromine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
155. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
156. the method for claim 91, wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
157. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
158. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
159. the method for claim 91, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
160. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
161. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
162. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
163. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
164. the method for claim 91, wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
165. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
166. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
167. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
168. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
169. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
170. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
171. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
172. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
173. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
174. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
175. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
176. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
177. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
178. the method for claim 91, wherein X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
179. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N ,-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
180. the method for claim 91, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
181. the method for flow process 4 expressions:
Flow process 4
Wherein
X represents I, Br, Cl, alkyl sulfonic ester, or aromatic yl sulphonate;
Z represents the aryl that replaces, heteroaryl or alkenyl non-imposedly;
L represents H or negative charge;
Catalyzer comprises copper atom or ion, and ligand;
Alkali is represented brnsted base;
R represents hydrogen, the alkyl that replaces, cycloalkyl, aralkyl, aryl, or heteroaryl non-imposedly;
R ' represents hydrogen, alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl, formyl radical, acyl group ,-CO respectively independently 2R " ,-C (O) N (R) 2, alkylsulfonyl ,-P (O) (OR ") 2,-CN, or-NO 2
R " represent non-imposed ground substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl respectively independently; And
C (R ') 2(R) can represent nitrile altogether.
182. the method for claim 181, wherein X represents iodine.
183. the method for claim 181, wherein X represents bromine.
184. the method for claim 181, wherein X represents chlorine.
185. the method for claim 181, wherein the ligand that comprises of catalyzer is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
186. the method for claim 181, wherein the ligand that comprises of catalyzer is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
187. the method for claim 181, wherein the ligand that comprises of catalyzer is selected from 2-phenylphenol, 2, the 2-isopropyl-phenol, 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
188. the method for claim 181, wherein the ligand that comprises of catalyzer is a chelating ligand.
189. the method for claim 181, wherein the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
190. claim 181 method, wherein the ligand that comprises of catalyzer is cis-1, the 2-diamino-cyclohexane, instead-1,2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1, the 2-diamino-cyclohexane, anti--N, N '-dimethyl-1, the 2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1.
191. the method for claim 181, wherein the ligand that comprises of catalyzer is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
192. the method for claim 181,, wherein alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
193. the method for claim 181, wherein alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
194. the method for claim 181, wherein catalyzer is less than or equal to about 10mol% with respect to the amount of Z-X.
195. the method for claim 181, wherein catalyzer is less than or equal to about 5mol% with respect to the amount of Z-X.
196. the method for claim 181, wherein catalyzer is less than or equal to about 1mol% with respect to the amount of Z-X.
197. the method for claim 181, wherein catalyzer is less than or equal to about 0.1mol% with respect to the amount of Z-X.
198. the method for claim 181, wherein this method temperature of carrying out is less than about 150 ℃.
199. the method for claim 181, wherein this method temperature of carrying out is less than about 140 ℃.
200. the method for claim 181, wherein this method temperature of carrying out is less than about 110 ℃.
201. the method for claim 181, wherein this method temperature of carrying out is less than about 100 ℃.
202. the method for claim 181, wherein this method temperature of carrying out is less than about 90 ℃.
203. the method for claim 181, wherein this method temperature of carrying out is less than about 50 ℃.
204. the method for claim 181, wherein this method temperature of carrying out is less than about 40 ℃.
205. the method for claim 181, wherein this method is carried out at ambient temperature.
206. the method for claim 181, wherein Z represents the aryl that replaces non-imposedly.
207. the method for claim 181, wherein Z represents the phenyl that replaces non-imposedly.
208. the method for claim 181, wherein R represents H.
209. the method for claim 181, wherein R ' represents acyl group independently, or-CO 2R ".
210. the method for claim 181, wherein R " represent alkyl, cycloalkyl, or aralkyl independently.
211. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
212. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
213. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
214. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is a chelating ligand.
215. the method for claim 181, wherein X represents iodine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
216. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
217. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
218. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
219. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
220. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
221. the method for claim 181, wherein X represents I; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
222. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
223. the method for claim 181, wherein X represents I; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
224. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
225. the method for claim 181, wherein X represents iodine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
226. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
227. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
228. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
229. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
230. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
231. the method for claim 181, wherein X represents iodine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
232. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
233. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
234. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
235. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand.
236. the method for claim 181, wherein X represents bromine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
237. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
238. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
239. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
240. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
241. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
242. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
243. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
244. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
245. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
246. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
247. the method for claim 181, wherein X represents bromine; And the ligand that comprises of catalyzer is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
248. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
249. the method for claim 181, wherein X represents bromine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
250. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
251. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
252. the method for claim 181, wherein X represents bromine; The ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
253. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline.
254. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is the phenol that replaces non-imposedly, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane.
255. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1, the 10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-chloro-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid.
256. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand.
257. the method for claim 181, wherein X represents chlorine; And the ligand that comprises of catalyzer be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1.
258. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1.
259. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1.
260. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted aryl alcohol, alkylamine, and 1, the 2-diamines, 1, the 2-amino alcohol, 1, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
261. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is a non-imposed ground substituted phenol, 1, and the 2-diamino-cyclohexane, or 1,2-diamino alkane; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
262. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-iodo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
263. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is a chelating ligand; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
264. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises be replace non-imposedly 1,2-diamino-cyclohexane, 1,10-phenanthroline, colamine, or 1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
265. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N-tolyl-1, the 2-diamino-cyclohexane, anti--N-tolyl-1, the 2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
266. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is carbonate, phosphoric acid salt, oxide compound, oxyhydroxide, alkoxide, phenates, amine, metal amide, fluorochemical, or guanidine.
267. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
268. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is the phenol of the replacement that replaces non-imposedly, 1, and 2-diamino-cyclohexane, 1,2-amino-alkane; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
269. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is selected from the 2-phenylphenol, 2,2-isopropyl-phenol, the 1-naphthols, oxine, 8-quinolylamine, DBU, 2-(dimethylamino) ethanol, ethylene glycol, N, N-diethyl salicyl acid amides, 2-(dimethylamino) glycine, N, N, N ', N '-tetramethyl--1,1,10-phenanthroline, 10-phenylbenzene-1, the 10-phenanthroline, 10-dimethyl-1,10-phenanthroline, the 5-methyl isophthalic acid, 10-phenanthroline, 5-bromo-1, the 10-phenanthroline, 5-nitro-1,10-phenanthroline, 4-(dimethylamino) pyridine, 2-(aminomethyl) pyridine and (methyl-imino) etheric acid; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate sodium tert-butoxide, or sodium hydroxide.
270. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is a chelating ligand; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
271. the method for claim 181, wherein X represents chlorine; The ligand that catalyzer comprises is the aryl alcohol that replaces non-imposedly, alkylamine, and the 2-diamines, the 2-amino alcohol, the 2-glycol, carbene imidazoles  salt, pyridine, or 1, the 10-phenanthroline; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
272. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, cis-N ,-tolyl-1,2-diamino-cyclohexane, instead-and N-tolyl-1,2-diamino-cyclohexane, cis-and anti--N-tolyl-1, the mixture of 2-diamino-cyclohexane, thanomin, 1, the 2-diaminoethanes, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
273. the method for claim 181, wherein X represents chlorine; And the ligand that catalyzer comprises is cis-1,2-diamino-cyclohexane, anti--1, the 2-diamino-cyclohexane, cis-and anti--1, the mixture of 2-diamino-cyclohexane, cis-N, N '-dimethyl-1,2-diamino-cyclohexane, instead-and N, N '-dimethyl-1,2-diamino-cyclohexane, cis-and anti--N, N '-dimethyl-1, the mixture of 2-diamino-cyclohexane, or N, N '-dimethyl-1; And alkali is potassiumphosphate, salt of wormwood, cesium carbonate, sodium tert-butoxide, or sodium hydroxide.
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